Concise Review: Embryonic Stem Cells: A New Tool to Study Osteoblast and Osteocl - 《stemcells》干细胞学杂志干细胞之家



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作者：Laurence Duplomba,b, Maylis Dagouassatc, Philippe Jourdonc, Dominique Heymanna,b作者单位：aLaboratoire de Physiopathologie de la Rsorption Osseuse et Thrapie des Tumeurs Osseuses Primitives, INSERM, ERI , Nantes, France; + @( \/ @2 a( d0 h- R; K2 J

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      【摘要】" I5 w# z2 z; N, L: a
   Bone remodeling involves synthesis of organic matrix by osteoblasts and bone resorption by osteoclasts. A tight collaboration between these two cell types is essential to maintain a physiological bone homeostasis. Thus, osteoblasts control bone-resorbing activities and are also involved in osteoclast differentiation. Any disturbance between these effectors leads to the development of skeletal abnormalities and/or bone diseases. In this context, the determination of key genes involved in bone cell differentiation is a new challenge to treat any skeletal disorders. Different models are used to study the differentiation process of these cells, but all of them use pre-engaged progenitor cells, allowing us to study only the latest stages of the differentiation. Embryonic stem (ES) cells come from the inner mass of the blastocyst prior its implantation to the uterine wall. Because of their capacity to differentiate into all germ layers, and so into all tissues of the body, ES cells represent the best model by which to study earliest stages of bone cell differentiation. Osteoblasts are generated by two methods, one including the generation of embryoid body, the other not. Mineralizing cells are obtained after 2 weeks of culture and express all the specific osteoblastic markers (alkaline phosphatase, type I collagen, osteocalcin, and others). Osteoclasts are generated from a single-cell suspension of ES cells seeded on a feeder monolayer, and bone-resorbing cells expressing osteoclastic markers such as tartrate-resistant alkaline phosphatase or receptor activator of nuclear factor B are obtained within 11 days. The aim of this review is to present recent discoveries and advances in the differentiation of both osteoblasts and osteoclasts from ES cells.
      【关键词】 Embryonic stem cells Embryoid bodies Osteoblasts Osteoclasts( G2 l1 p; k  F
   INTRODUCTION

Bone is a specialized connective tissue with elastic and strength properties. Bone tissue has various functions, including mechanical properties (offering the site and support for insertion of skeletal muscle tissue), protective properties for vital organs (heart, brain, bone marrow, etc.), and a pivotal metabolic function. Indeed, bone mineral matrix represents the main reserve of mineral ions, especially calcium and phosphate. Bone is composed of two main cell populations (osteoblast and osteoclast lineages) and extracellular matrix-associating organic (noncollagen proteins, such as fibronectin, and growth factors, collagen types I and III, etc.) and mineral (hydroxyapatite crystals) phases. Bone undergoes cyclic modifications, named bone remodeling, that allow for adaptation to mechanical constraints and maintain homeostasis of phosphorus and calcium. These cyclic modifications correspond to coordinated phases of bone formation by osteoblasts . Furthermore, any disruption in this balance results in pathological states leading to increase (i.e., osteopetrosis) or loss (osteolytic diseases and osteoporosis) of bone mass.# \$ u) M; F" j, h  o
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Embryonic stem (ES) cells come from the inner mass of the blastocyst prior to implantation into the uterine wall. ES cells have important characteristics: they are pluripotent, meaning that a single cell has the capability of developing cells of all germ layers (endoderm, ectoderm, and mesoderm) and can give rise to all tissues of the body. From the ectoderm, ES cells can generate cells of skin, brain, eyes, and neural tissue. From the mesoderm, they can generate bone, cartilage, muscle, heart, or kidneys, and from the endoderm, they can generate liver, pancreas, thymus, thyroid, lung, and so on. ES cells have the potential of long-self renewal in vitro and can be induced to differentiate with appropriate culture conditions and specific factors. In addition to their potential interest in regenerating bone tissue by transplantation, ES cells offer a strong advantage in fundamental research by permitting the study of osteoblast and osteoclast differentiations from the earliest differentiation state of the cell. Indeed, the other models in the literature (and described below) use cells already pre-engaged, and so early steps of the differentiation could not be studied. Furthermore, ES cells are the best model to study the differentiation into mesenchymal cells that give rise to osteoblasts. ES cells are thought to be a powerful system to decipher the molecular mechanisms involved in both osteoblast and osteoclast differentiation, and so from the earlier to the later stages of the differentiation. The present review focuses on the recent advances concerning osteoblast and osteoclast differentiation from ES cells.
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FROM ES CELLS TO OSTEOBLASTS
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Osteoblasts, which derive from the mesoderm, are cells that specialize in the production of extracellular matrix (which is mainly composed of type I collagen) and the mineralization process . Furthermore, MSC, as well as the calvaria model or MC3T3, can be considered osteoblastic progenitor cells or pre-engaged cells and so do not allow study of the early steps of osteoblastic differentiation. A new strategy is the use of ES cells, which are also considered new potential cells for transplantation.

Table 1. Main in vitro models described in the literature and used to study osteoblastic differentiation$ [. J, ^: V' H3 o! w7 p
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Many markers are used to estimate the differentiation level of the cells: core binding factor 1 (Cbfa1/Runx2), which is the main specific transcription factor involved in osteogenesis; type I collagen; osteopontin (OP); osteonectin; osteocalcin (OC); bone sialoprotein (BSP); and alkaline phosphatase (ALP), which may affect the mineralization. The capacity of osteoblasts to mineralize in vitro can be visualized by von Kossa or Alizarin red staining. In vitro differentiation of ES cells into osteoblasts needs the addition of several factors, which in vivo are released by cells from the microenvironment of osteoblasts. Among these factors, ascorbic acid and 1,25-OH vitamin D3 are mandatory for matrix deposition and mineralization, which are visualized as hydroxyapatite-containing mineral nodules when a source of organic phosphate is added to the culture (for example, ¦Â-glycerophosphate). This osteogenic medium has already been shown to induce osteoblast formation from human MSC .- ]- O9 _' U0 m* T

Different mouse ES cells line are used to generate osteoblasts: D3  but inhibits cardiogenesis, indicating that retinoic acid alters mesoderm formation in EBs. Thus, the role of retinoic acid appears to be crucial during the first stages of the culture, after EB formation but before differentiation.
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Figure 1. Differentiation of osteoblasts from ES cells. 750 R1 ES cells (provided by Dr. Nagy, Samuel Lunenfeld Research Institute, Toronto, ON, Canada) were seeded in a 20-µl drop on the inner side of the cover of a bacteriological Petri dish filled with PBS and incubated at 37¡ãC with 5% CO2. ES cells condensed by gravitational force into a three-dimensional sphere called the EB. After 2 days, EBs were transferred to a new bacteriological Petri dish and allowed to growth in suspension for 3 more days in culture medium. At day 5, EBs were plated in a 24-well plate (two or three EBs per well) in the presence or absence of osteogenic factors (50 µg/ml ascorbic acid, 10 mM ¦Â-glycerophosphate, 5 x 10¨C8 M 1,25-OH vitamin D3, and 10¨C8 M dexamethasone. At 30 days, the presence of osteoblasts was confirmed by mineralization staining and by reverse transcription-polymerase chain reaction analysis of the expression of specific osteoblastic markers, shown on the upper arrow. Abbreviations: ALP, alkaline phosphatase; BSP, bone sialoprotein; Cbfa 1, core binding factor 1; Coll I, type I collagen; D, day; ES, embryonic stem; OC, osteocalcin; OP, osteopontin; PBS, phosphate-buffered saline.6 [  Y/ a6 y; B9 \
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Figure 2. Embryoid body at day 6, after plating for differentiation (A) and Alizarin red staining (B). (A): EB was generated by the hanging drop culture method, as described in Fig. 1. (B): Mineralization was visualized by Alizarin red staining after 30 days of culture of R1 cells in presence of ascorbic acid, ¦Â-glycerophosphate, 1,25-OH vitamin D3, and dexamethasone. Magnification, x100.
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zur Nieden et al. studied the expression pattern of osteoblastic markers and their apparition during the differentiation of ES cells .

The effects of ascorbic acid, 1,25-OH vitamin D3, ¦Â-glycerophosphate, and dexamethasone have been studied in a temporal way. The addition of ascorbic acid, 1,25-OH vitamin D3, and ¦Â-glycerophosphate only during the formation of EBs does not induce the osteoblastic markers, and the best result is observed when these factors are added together after EB formation , could also be tested during the differentiation of ES cells. Furthermore, it will be interesting to know whether these factors could potentiate osteoblast differentiation as soon as the beginning of the process from the ES cells or whether they act in the later states of the differentiation, as with the pre-engaged models.
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Generation of osteoblast has also been studied in human ES (hES) cells . Indeed, primary bone-derived cells secrete BMP-2 and BMP-4, which are efficient to induce the ES cells differentiation, probably in combination with other pro-osteoblastic factors also secreted by the primary-bone cells but not yet characterized. Furthermore, cell-to-cell contacts with primary bone-derived cells may help the differentiation.  V% v7 @. k: c8 n* }# P1 S

Osteoblasts can also be produced from ES cell-generated MSC. Indeed, two recent studies provided a model to generate MSC from human ES cells . By adding this "MSC step" to the differentiation process, these protocols permit large amounts of pure MSC to be obtained and consequently increase the number of osteoblasts obtained from these MSC and suitable for therapeutic applications. Moreover, these ES cell-derived MSC have the capacity to support the growth of undifferentiated ES cells, which is a real advance in stem cell research because it provides a source of autologous feeder for the culture of ES cells, which considerably increases the possibility of creating secure ES cells banks for therapeutic use.6 c; \! N  y3 h$ x5 ~+ |( p
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Differentiation of mouse or human ES cells into osteoblasts is effective. Different approaches are used to achieve osteogenic differentiation: with or without EB generation and with various osteogenic molecules. Further work is needed to elucidate the potential role of other cytokines that could enhance osteogenic differentiation.

FROM ES CELLS TO OSTEOCLASTS

Osteoclasts are bone resorbing cells that derive from the hematopoietic mesodermal lineage. Different models, presented in Table 2, have been developed to study osteoclast differentiation: bone marrow/spleen cells with or without osteoblastic/stromal cells .
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Table 2. Main in vitro models developed to study osteoclastic differentiation' ]& X2 x& b& z" z- l

A few studies report the generation of osteoclasts from ES cells. The mouse ES cells used are D3 . As for osteoblasts, osteoclasts can be generated efficiently from ES cells. The multistep culture is a good model by which to investigate the mechanisms and the chronological apparition of specific markers, as each different step of the culture corresponds to a different stage of the differentiation.( d* \8 L9 t& n4 J
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Figure 3. Protocols used to generate osteoclasts. A single-cell suspension of ES cells was cultured on ST2 or OP9 cell lines, with one- or multistep culture as described in the text. Cells were cultured in the presence or absence of 10¨C8 M VD3 and 10¨C7 M Dex. Generation of osteoclasts occurs around 11¨C14 days and is characterized by TRAP staining and RT-PCR. Abbreviations: D, day; Dex, dexamethasone; ES, embryonic stem; OP, osteopontin; RT-PCR, reverse transcription-polymerase chain reaction; TRAP, tartrate-resistant alkaline phosphatase; VD3, 1,25-OH vitamin D3.

Figure 4. Tartrate-resistant alkaline phosphatase (TRAP) staining after 11 days on a one-step culture on ST2 cell line. Colonies () obtained from R1 ES cells were cultured on the ST2 monolayer (*). (A): Control conditions; no TRAP staining is observed. (B): tartrate-resistant alkaline phosphatase-positive osteoclasts in the presence of 10¨C8 M 1,25-OH vitamin D3 and 10¨C7 M dexamethasone, as described by Hemmi et al. . Magnification, x100.7 I. |/ M5 R  B' {1 U! w
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Figure 5. Osteoclastogenesis from ES cells to mature osteoclasts. Schema showing chronological apparition of some specific osteoclastic markers (above the arrow) and some factors involved in the differentiation (as described by Tsuneto et al. ). Abbreviations: CTR, calcitonin receptor; ES, embryonic stem; M-CSF, macrophage-colony-stimulating factor; RANK, receptor activator of nuclear factor B; RANKL, receptor activator of nuclear factor B ligand; TRAP, tartrate-resistant alkaline phosphatase.

All these studies help us better understand the molecular mechanisms of osteoclastogenesis and so elucidate deregulated events happening during a tumoral process. Furthermore, differentiation of ES cells into osteoclasts is promising for therapy. For example, transplantation of ES cell-generated osteoclasts could be envisaged to cure some pathologies, such as osteoclast-poor osteopetrosis, which is a rare genetic disorder characterized by severely reduced bone resorption due to a defect in osteoclast development. Presently, the treatment for this pathology, consisting of engraftment of hematopoietic stem cells, fails .
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PERSPECTIVES

The treatment of osteoporosis, as well as other osteolytic bone diseases, is mainly based on bisphosphonate drugs, which are inhibitors of osteoclast-mediated bone resorption  into osteoblasts, first by inducing mesodermal differentiation and then by inducing the osteoblast lineage specifically.* m  X7 C; D+ e1 M8 R5 V  W
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The differentiation of osteoclasts from ES cells is also effective. It is interesting to note that generation of osteoblasts and osteoclasts could be realized with the same differentiating factors (dexamethasone and 1,25-OH vitamin D3, with or without ascorbic acid). The main difference between the two differentiations is the generation of EBs for osteoblasts (except in one study), which is not used to generate osteoclasts. For osteoclastogenesis, one possibility to explain this difference is the production of RANKL by ST2 cells upon dexamethasone stimulation and 1,25-OH vitamin D3 stimulation . Furthermore, some cell-to-cell contacts between ES cells and ST2/OP9 cells could also be crucial for the differentiation into osteoclasts. In conclusion, ES cells are the best tool to understand molecular mechanisms involved in osteoblast and osteoclast differentiations, and particularly during the earliest stages of the differentiation. Indeed, other models used to generate bone cells are realized with pre-engaged cells and so omit the earliest phases of the differentiation. ES cells are also a good model to understand the mechanisms involved during mesenchymal cell differentiation that then give rise to osteoblasts or other cell types, such as adipocytes. As osteogenic factors or adipogenic factors are added since the beginning of the culture of ES cells, it could be envisaged that different populations of mesenchymal cells can emerge from ES cells. Furthermore, ES cells are also the best model to uncover the mechanisms involved in mesenchymal cell differentiation or other kind of cells, such as cells of the hematopoietic lineage.% l9 w$ P1 E7 V" f. F
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Even if some studies should be performed to decipher all the signals that influence osteoblast differentiation and to control all the necessary steps for a successful transplantation, ES cells, as well as MSC, are promising in regenerative medicine. ES cells also offer the possibility of finding new key genes involved in the differentiation program and consequently those that can be deregulated during a tumoral process. In this way, ES cells represent a positive approach to find new target genes for bone cancer treatment and other bone disease therapies.

DISCLOSURES

The authors indicate no potential conflicts of interest.6 w/ P. ]4 k4 |1 s1 P) y
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ACKNOWLEDGMENTS$ A! f- }' _8 y2 ]* g5 p/ l4 O- U
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L.D. is supported by an Association pour la Recherche sur le Cancer postdoctoral fellowship.! i* b8 H" u- g  a2 C5 {
      【参考文献】

Aguila HL, Rowe DW. Skeletal development, bone remodeling, and hematopoiesis. Immunol Rev 2005;208:7¨C18.7 U) v! q; }8 _+ {, ?1 M# i

Rousselle AV, Heymann D. Osteoclastic acidification pathways during bone resorption. Bone 2002;30:533¨C540.
, `4 r2 r9 _5 @; J6 V- Y
Aubin JE, Triffit JT. Mesenchymal stem cells and osteoblast differentiation. In: Bilezikian JP, Raisz LG, Rodan GA, eds. Principles of Bone Biology.San Diego: Academic Press,2002;Vol. 1:59¨C81.8 f5 \6 F8 n! U0 h0 h

Chambers TJ. Regulation of the differentiation and function of osteoclasts. J Pathol 2000;192:4¨C13.
* T: H/ H  f/ _
Roodman GD. Regulation of osteoclast differentiation. Ann N Y Acad Sci 2006;1068:100¨C109.& b1 x! m. Z( d. U" K5 ]8 l' @

Epker BN, Frost HM. Correlation of bone resorption and formation with the physical behavior of loaded bone. J Dent Res 1965;44:33¨C41.6 P, ?+ s  F& h' |3 Q" a0 y. B6 N

Ilvesaro J, Tuukkanen J. Gap-junctional regulation of osteoclast function. Crit Rev Eukaryot Gene Expr 2003;13:133¨C146.

Heymann D, Guicheux J, Gouin F et al. Cytokines, growth factors and osteoclasts. Cytokine 1998;10:155¨C168.$ w, g0 w. \9 c  k. H7 {( f

Theoleyre S, Wittrant Y, Tat SK et al. The molecular triad OPG/RANK/RANKL: Involvement in the orchestration of pathophysiological bone remodeling. Cytokine Growth Factor Rev 2004;15:457¨C475.
* P7 D/ ?4 F( g8 o4 h. {
Blair HC, Zaidi M, Schlesinger PH. Mechanisms balancing skeletal matrix synthesis and degradation. Biochem J 2002;364:329¨C341.) N' f% m% ^- g  H

Ishimi Y, Miyaura C, Jin CH et al. IL-6 is produced by osteoblasts and induces bone resorption. J Immunol 1990;145:3297¨C3303.
& q4 m" f2 b, q! v' @& T: r+ _- X
Marie PJ, Hott M, Launay JM et al. In vitro production of cytokines by bone surface-derived osteoblastic cells in normal and osteoporotic postmenopausal women: Relationship with cell proliferation. J Clin Endocrinol Metab 1993;77:824¨C830.

Lowik CW, van der Pluijm G, Bloys H et al. Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: A possible role of interleukin-6 in osteoclastogenesis. Biochem Biophys Res Commun 1989;162:1546¨C1552.
  \7 ?1 Z$ n" \' P: |
Liu XH, Kirschenbaum A, Yao S et al. Cross-talk between the interleukin-6 and prostaglandin E(2) signaling systems results in enhancement of osteoclastogenesis through effects on the osteoprotegerin/receptor activator of nuclear factor-kappaB (RANK) ligand/RANK system. Endocrinology 2005;146:1991¨C1998.8 P+ X7 E7 A: O4 a& X, R+ |$ h

Filanti C, Dickson GR, Di Martino D et al. The expression of metalloproteinase-2, -9, and -14 and of tissue inhibitors-1 and -2 is developmentally modulated during osteogenesis in vitro, the mature osteoblastic phenotype expressing metalloproteinase-14. J Bone Miner Res 2000;15:2154¨C2168.
- @1 i3 p6 o6 _& _- Y
Uchida M, Shima M, Shimoaka T et al. Regulation of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) by bone resorptive factors in osteoblastic cells. J Cell Physiol 2000;185:207¨C214.' @$ C; D3 U/ Y' A

Franz-Odendaal TA, Hall BK, Witten PE. Buried alive: How osteoblasts become osteocytes. Dev Dyn 2006;235:176¨C190.
, Z& Z. I6 u* b/ o
Sudo H, Kodama HA, Amagai Y et al. In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria. J Cell Biol 1983;96:191¨C198.
6 C. m3 g% c- ]: c0 H, f+ E
Kurihara N, Ikeda K, Hakeda Y et al. Effect of 1,25-dihydroxyvitamin D3 on alkaline phosphatase activity and collagen synthesis in osteoblastic cells, clone MC3T3¨CE1. Biochem Biophys Res Commun 1984;119:767¨C771.
7 U! D+ c- M; q
Kim SW, Her SJ, Park SJ et al. Ghrelin stimulates proliferation and differentiation and inhibits apoptosis in osteoblastic MC3T3¨CE1 cells. Bone 2005;37:359¨C369.

Nielsen LB, Pedersen FS, Pedersen L. Expression of type III sodium-dependent phosphate transporters/retroviral receptors mRNAs during osteoblast differentiation. Bone 2001;28:160¨C166.% Q# O  |! C8 L" ~; o" N/ [- t- z
  I0 q. H8 |7 _, W
Oshima K, Nampei A, Matsuda M et al. Adiponectin increases bone mass by suppressing osteoclast and activating osteoblast. Biochem Biophys Res Commun 2005;331:520¨C526.
* k( m  e! x# ^  [
Guicheux J, Lemonnier J, Ghayor C et al. Activation of p38 mitogen-activated protein kinase and c-Jun-NH2-terminal kinase by BMP-2 and their implication in the stimulation of osteoblastic cell differentiation. J Bone Miner Res 2003;18:2060¨C2068.9 i. x5 {# [4 a7 t- F  m
& r6 a7 u& Z! _+ Y3 L; ]
Boden SD, McCuaig K, Hair G et al. Differential effects and glucocorticoid potentiation of bone morphogenetic protein action during rat osteoblast differentiation in vitro. Endocrinology 1996;137:3401¨C3407.
( \/ X& Q/ m, n4 p9 \. W
Declercq H, Van den Vreken N, De Maeyer E et al. Isolation, proliferation and differentiation of osteoblastic cells to study cell/biomaterial interactions: Comparison of different isolation techniques and source. Biomaterials 2004;25:757¨C768.3 T! f! J1 y* f* X2 F2 `' k

Ikedo D, Ohishi K, Yamauchi N et al. Stimulatory effects of phenytoin on osteoblastic differentiation of fetal rat calvaria cells in culture. Bone 1999;25:653¨C660.4 a$ \% g& b  `9 y5 }

Johnson KA, Hessle L, Vaingankar S et al. Osteoblast tissue-nonspecific alkaline phosphatase antagonizes and regulates PC-1. Am J Physiol Regul Integr Comp Physiol 2000;279:R1365¨CR1377.
) i( s1 C7 t7 e, z6 n4 Z' `' e
Bi Y, Nielsen KL, Kilts TM et al. Biglycan deficiency increases osteoclast differentiation and activity due to defective osteoblasts. Bone 2006;38:778¨C786.
8 M0 s. l$ x9 r+ r2 i1 i5 i
Hattori H, Sato M, Masuoka K et al. Osteogenic potential of human adipose tissue-derived stromal cells as an alternative stem cell source. Cells Tissues Organs 2004;178:2¨C12.
; O7 @% w* \1 Z2 p) p; B  d
Lee RH, Kim B, Choi I et al. Characterization and expression analysis of mesenchymal stem cells from human bone marrow and adipose tissue. Cell Physiol Biochem 2004;14:311¨C324.

Fukuchi Y, Nakajima H, Sugiyama D et al. Human placenta-derived cells have mesenchymal stem/progenitor cell potential. STEM CELLS 2004;22:649¨C658.7 {5 @+ T$ e8 ^. e
. L; J. ~# s8 S
Alsalameh S, Amin R, Gemba T et al. Identification of mesenchymal progenitor cells in normal and osteoarthritic human articular cartilage. Arthritis Rheum 2004;50:1522¨C1532.

Bruder SP, Kurth AA, Shea M et al. Bone regeneration by implantation of purified, culture-expanded human mesenchymal stem cells. J Orthop Res 1998;16:155¨C162.7 W( f& v0 c: Q- @7 Y

Wang Z, Goh J, Das De S et al. Efficacy of bone marrow-derived stem cells in strengthening osteoporotic bone in a rabbit model. Tissue Eng 2006;12:1753¨C1761.

Toquet J, Rohanizadeh R, Guicheux J et al. Osteogenic potential in vitro of human bone marrow cells cultured on macroporous biphasic calcium phosphate ceramic. J Biomed Mater Res 1999;44:98¨C108.
) n0 Y% v- s9 R+ o3 R/ M
Bohic S, Rohanizadeh R, Touchais S et al. Leukemia inhibitory factor and oncostatin M influence the mineral phases formed in a murine heterotopic calcification model: A Fourier transform-infrared microspectroscopic study. J Bone Miner Res 1998;13:1619¨C1632.

Bonab MM, Alimoghaddam K, Talebian F et al. Aging of mesenchymal stem cell in vitro. BMC Cell Biol 2006;7:14.

Pittenger MF, Mackay AM, Beck SC et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143¨C147." n2 `) b/ l! M

Muraglia A, Cancedda R, Quarto R. Clonal mesenchymal progenitors from human bone marrow differentiate in vitro according to a hierarchical model. J Cell Sci 2000;113:1161¨C1166.
1 |+ {" m% ]9 i+ O/ |# I
Jaiswal N, Haynesworth SE, Caplan AI et al. Osteogenic differentiation of purified, culture-expanded human mesenchymal stem cells in vitro. J Cell Biochem 1997;64:295¨C312.  X/ W7 z7 p; P. d! ^2 M- w6 o: T( r

Olivier EN, Rybicki AC, Bouhassira EE. Differentiation of human embryonic stem cells into bipotent mesenchymal stem cells. STEM CELLS 2006;24:1914¨C1922.  b' S" I2 @& @+ o7 C; E% U

Buttery LD, Bourne S, Xynos JD et al. Differentiation of osteoblasts and in vitro bone formation from murine embryonic stem cells. Tissue Eng 2001;7:89¨C99.
( K5 v0 A. Y- J9 C! |4 U$ i
Kawaguchi J, Mee PJ, Smith AG. Osteogenic and chondrogenic differentiation of embryonic stem cells in response to specific growth factors. Bone 2005;36:758¨C769.  X" W5 y6 F5 o$ ?6 Q7 m

Cheng SL, Yang JW, Rifas L et al. Differentiation of human bone marrow osteogenic stromal cells in vitro: Induction of the osteoblast phenotype by dexamethasone. Endocrinology 1994;134:277¨C286.  A5 b, g/ x$ v8 S1 i# ~( G

zur Nieden NI, Kempka G, Ahr HJ. In vitro differentiation of embryonic stem cells into mineralized osteoblasts. Differentiation 2003;71:18¨C27.

zur Nieden NI, Kempka G, Rancourt DE et al. Induction of chondro-, osteo- and adipogenesis in embryonic stem cells by bone morphogenetic protein-2: Effect of cofactors on differentiating lineages. BMC Dev Biol 2005;5:1.& `' v" u) t3 C& s+ B$ n

Phillips BW, Belmonte N, Vernochet C et al. Compactin enhances osteogenesis in murine embryonic stem cells. Biochem Biophys Res Commun 2001;284:478¨C484.% Y* r# A; a. Q' C5 D. Y0 N, B

Bronson SK. Bone nodule formation via in vitro differentiation of murine embryonic stem cells. Methods Enzymol 2003;365:241¨C251./ Z+ a( q2 Q5 `7 H2 c8 X+ ^. y
) r7 k: c2 k0 A  z' ^
Bain G, Kitchens D, Yao M et al. Embryonic stem cells express neuronal properties in vitro. Dev Biol 1995;168:342¨C357., K! p- ~( L( @" d' m

Dani C, Smith AG, Dessolin S et al. Differentiation of embryonic stem cells into adipocytes in vitro. J Cell Sci 1997;110:1279¨C1285.* O8 m6 D8 [- I  W3 Y
, n( q+ v  T4 R6 P- D3 }& i
Choi JY, Lee BH, Song KB et al. Expression patterns of bone-related proteins during osteoblastic differentiation in MC3T3¨CE1 cells. J Cell Biochem 1996;61:609¨C618.2 b9 @9 ?3 |) |$ p; S

Yamaguchi A, Katagiri T, Ikeda T et al. Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro. J Cell Biol 1991;113:681¨C687.0 R3 B8 w. ^# C
2 E2 y- Z6 z1 I" q/ v- g& I) r2 _1 S% u
Kramer J, Hegert C, Guan K et al. Embryonic stem cell-derived chondrogenic differentiation in vitro: Activation by BMP-2 and BMP-4. Mech Dev 2000;92:193¨C205.4 A5 K# e9 `/ r# F) s+ h; o' [) q

Valta MP, Hentunen T, Qu Q et al. Regulation of osteoblast differentiation: A novel function for fibroblast growth factor 8. Endocrinology 2006;147:2171¨C2182.9 C+ ]4 Z: b* ~% R3 |7 r" M4 r# z3 Q

Karp JM, Ferreira LS, Khademhosseini A et al. Cultivation of human embryonic stem cells without the embryoid body step enhances osteogenesis in vitro. STEM CELLS 2006;24:835¨C843.
7 p! ~; X0 n& \: W* M2 `" }. K7 j
Sottile V, Thomson A, McWhir J. In vitro osteogenic differentiation of human ES cells. Cloning Stem Cells 2003;5:149¨C155.5 m8 S' `. j8 N; J6 {

Cao T, Heng BC, Ye CP et al. Osteogenic differentiation within intact human embryoid bodies result in a marked increase in osteocalcin secretion after 12 days of in vitro culture, and formation of morphologically distinct nodule-like structures. Tissue Cell 2005;37:325¨C334.9 ^) m+ e* e' ^) [( v+ T- V

Ahn SE, Kim S, Park KH et al. Primary bone-derived cells induce osteogenic differentiation without exogenous factors in human embryonic stem cells. Biochem Biophys Res Commun 2006;340:403¨C408.
: Q# w0 V0 n$ J4 Z
Barberi T, Willis LM, Socci ND et al. Derivation of multipotent mesenchymal precursors from human embryonic stem cells. PLoS Med 2005;2:e161.2 K7 X4 K" {: T' u/ d

Yamashita A, Takada T, Narita J et al. Osteoblastic differentiation of monkey embryonic stem cells in vitro. Cloning Stem Cells 2005;7:232¨C237.
9 T' H" i' F& f! g+ m7 k0 P, @0 {
Fuller K, Chambers TJ. Generation of osteoclasts in cultures of rabbit bone marrow and spleen cells. J Cell Physiol 1987;132:441¨C452.# O; N$ g5 L0 l; Y
- o. R* G" Y+ i% X+ _9 j$ y
Udagawa N, Takahashi N, Katagiri T et al. Interleukin (IL)-6 induction of osteoclast differentiation depends on IL-6 receptors expressed on osteoblastic cells but not on osteoclast progenitors. J Exp Med 1995;182:1461¨C1468.
  j# c9 s! |- R0 u+ l
Nishikawa M, Akatsu T, Katayama Y et al. Bisphosphonates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone 1996;18:9¨C14.$ ?+ g( o8 y9 H' }7 {

Sabokbar A, Fujikawa Y, Brett J et al. Increased osteoclastic differentiation by PMMA particle-associated macrophages. Inhibitory effect by interleukin 4 and leukemia inhibitory factor. Acta Orthop Scand 1996;67:593¨C598.
2 Y- O) {( H+ p3 A% P' @
O'Brien EA, Williams JH, Marshall MJ. Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria. Biochem Biophys Res Commun 2000;274:281¨C290.7 T! Z( J2 b3 O% S
- `- J" L  T1 R  Y. K
Tsurukai T, Udagawa N, Matsuzaki K et al. Roles of macrophage-colony stimulating factor and osteoclast differentiation factor in osteoclastogenesis. J Bone Miner Metab 2000;18:177¨C184.
# H/ ]% X2 h$ h0 {1 x' A" d# N5 ^
Nicholson GC, Malakellis M, Collier FM et al. Induction of osteoclasts from CD14-positive human peripheral blood mononuclear cells by receptor activator of nuclear factor kappaB ligand (RANKL). Clin Sci (Lond) 2000;99:133¨C140.* }7 n9 G4 O4 h6 j+ r; E

Kudo O, Sabokbar A, Pocock A et al. Interleukin-6 and interleukin-11 support human osteoclast formation by a RANKL-independent mechanism. Bone 2003;32:1¨C7.# T' U9 i* D5 t) T

Beeton CA, Bord S, Ireland D et al. Osteoclast formation and bone resorption are inhibited by megakaryocytes. Bone 2006;24:24.

Sorensen MG, Henriksen K, Dziegiel MH et al. Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts. DNA Cell Biol 2006;25:475¨C483.* N  ^( H4 L9 Z% n/ Y4 S3 @& ]

Atkins GJ, Kostakis P, Vincent C et al. RANK expression as a cell surface marker of human osteoclast precursors in peripheral blood, bone marrow, and giant cell tumors of bone. J Bone Miner Res 2006;21:1339¨C1349.
- m6 ^2 I6 ]7 n: E5 M' P8 u6 ~
Wittrant Y, Theoleyre S, Couillaud S et al. Relevance of an in vitro osteoclastogenesis system to study receptor activator of NF-kB ligand and osteoprotegerin biological activities. Exp Cell Res 2004;293:292¨C301.4 X5 X0 A- K0 g. w6 U/ l
4 ^* d% I9 j" U# q: Q7 ]
Tanaka S, Takahashi N, Udagawa N et al. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J Clin Invest 1993;91:257¨C263.

Yasuda H, Shima N, Nakagawa N et al. Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 1998;95:3597¨C3602.

Perkins SL, Kling SJ. Local concentrations of macrophage colony-stimulating factor mediate osteoclastic differentiation. Am J Physiol 1995;269:E1024¨CE1030.
) X2 [4 P( ~: j3 [3 j
Shih C, Bernard GW. Peripheral blood mononuclear cells develop into multinucleated osteoclasts in tissue culture. Anat Rec 1996;245:41¨C45.6 s+ Q2 s* `% e& s. S1 X
3 A  X1 s5 J" e
Yamane T, Kunisada T, Yamazaki H et al. Development of osteoclasts from embryonic stem cells through a pathway that is c-fms but not c-kit dependent. Blood 1997;90:3516¨C3523.) l. @: Z% S! P& {7 R  n7 Q

Okuyama H, Tsuneto M, Yamane T et al. Discrete types of osteoclast precursors can be generated from embryonic stem cells. STEM CELLS 2003;21:670¨C680.
. O2 Q  s$ w3 U: X$ @
Hemmi H, Okuyama H, Yamane T et al. Temporal and spatial localization of osteoclasts in colonies from embryonic stem cells. Biochem Biophys Res Commun 2001;280:526¨C534.$ q9 ~- {& ?1 j4 h( Q8 _& g" E$ E
, z; f, \+ R% A& c5 f0 ~
Yamane T, Kunisada T, Yamazaki H et al. Sequential requirements for SCL/tal-1, GATA-2, macrophage colony-stimulating factor, and osteoclast differentiation factor/osteoprotegerin ligand in osteoclast development. Exp Hematol 2000;28:833¨C840., d  a- E; _4 f* ^/ F; h

Tsuneto M, Yamazaki H, Yoshino M et al. Ascorbic acid promotes osteoclastogenesis from embryonic stem cells. Biochem Biophys Res Commun 2005;335:1239¨C1246.) H. a$ d. H$ ~  q# r, Q

Nakano T, Kodama H, Honjo T. Generation of lymphohematopoietic cells from embryonic stem cells in culture. Science 1994;265:1098¨C1101.) e# T3 k. z8 h

Nicholls BM, Bredius RG, Hamdy NA et al. Limited rescue of osteoclast-poor osteopetrosis after successful engraftment by cord blood from an unrelated donor. J Bone Miner Res 2005;20:2264¨C2270.
" \$ E3 M4 [  A& l5 ^& h, b6 J/ p
Heymann D, Ory B, Gouin F et al. Bisphosphonates: New therapeutic agents for the treatment of bone tumors. Trends Mol Med 2004;10:337¨C343.* u. N7 G2 M9 O  o8 R2 m; p
3 h3 q4 e/ E) G
Alsberg E, Anderson KW, Albeiruti A et al. Cell-interactive alginate hydrogels for bone tissue engineering. J Dent Res 2001;80:2025¨C2029.$ w. {. t+ t8 t0 F: o
; c/ J4 t5 h/ r* H
Hattersley G, Chambers TJ. Effects of interleukin 3 and of granulocyte-macrophage and macrophage colony stimulating factors on osteoclast differentiation from mouse hemopoietic tissue. J Cell Physiol 1990;142:201¨C209.* g( M1 X3 S2 w* |# B4 C  q+ I% y
$ Q! `# S$ `; y3 j
Fischer EM, Layrolle P, Van Blitterswijk CA et al. Bone formation by mesenchymal progenitor cells cultured on dense and microporous hydroxyapatite particles. Tissue Eng 2003;9:1179¨C1188.
+ L0 A( u" ?6 S% d9 ^
Oreffo RO, Driessens FC, Planell JA et al. Growth and differentiation of human bone marrow osteoprogenitors on novel calcium phosphate cements. Biomaterials 1998;19:1845¨C1854.+ h8 R( P1 L- S0 |2 @

Yoshikawa H, Myoui A. Bone tissue engineering with porous hydroxyapatite ceramics. J Artif Organs 2005;8:131¨C136.
$ J, n. k( m# B3 }
Suzuki A, Raya A, Kawakami Y et al. Nanog binds to Smad1 and blocks bone morphogenetic protein-induced differentiation of embryonic stem cells. Proc Natl Acad Sci U S A 2006;103:10294¨C10299.' s  a/ y/ U9 U( ?

Nishimura R, Kato Y, Chen D et al. Smad5 and DPC4 are key molecules in mediating BMP-2-induced osteoblastic differentiation of the pluripotent mesenchymal precursor cell line C2C12. J Biol Chem 1998;273:1872¨C1879.( N4 @* q2 W  U5 X0 O! p

Ryoo HM, Lee MH, Kim YJ. Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 2006;366:51¨C57.
! U) g( P- F8 B5 T. c
Yasuda H, Shima N, Nakagawa N et al. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): A mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 1998;139:1329¨C1337.
0 l! ]+ ]) B6 Q, {. C8 j( o
Tu Q, Valverde P, Chen J. Osterix enhances proliferation and osteogenic potential of bone marrow stromal cells. Biochem Biophys Res Commun 2006;341:1257¨C1265.

Deliloglu-Gurhan SI, Vatansever HS, Ozdal-Kurt F et al. Characterization of osteoblasts derived from bone marrow stromal cells in a modified cell culture system. Acta Histochem 2006;108:49¨C57.
1 U  N$ i* N6 R9 N. u
van den Dolder J, Jansen JA. Enrichment of osteogenic cell populations from rat bone marrow stroma. Biomaterials 2007;28:249¨C255.
. }" G. i. U1 R- X9 I9 z) U/ L
Ye CP, Heng BC, Liu H et al. Culture media conditioned by heat-shocked osteoblasts enhances the osteogenesis of bone marrow-derived mesenchymal stromal cells. Cell Biochem Funct 2006; .

Kim SJ, Cho HH, Kim YJ et al. Human adipose stromal cells expanded in human serum promote engraftment of human peripheral blood hematopoietic stem cells in NOD/SCID mice. Biochem Biophys Res Commun 2005;329:25¨C31.
1 ]# g8 U' y# f1 L/ W
Malladi P, Xu Y, Yang GP et al. Functions of vitamin D, retinoic acid, and dexamethasone in mouse adipose-derived mesenchymal cells. Tissue Eng 2006;12:2031¨C2040.8 j  q1 @4 t1 f( M) c3 G

Tholpady SS, Katz AJ, Ogle RC. Mesenchymal stem cells from rat visceral fat exhibit multipotential differentiation in vitro. Anat Rec A Discov Mol Cell Evol Biol 2003;272:398¨C402.9 o" o& _) g) |/ F9 `

In 't Anker PS, Scherjon SA, Kleijburg-van der Keur C et al. Isolation of mesenchymal stem cells of fetal or maternal origin from human placenta. STEM CELLS 2004;22:1338¨C1345.

Kurihara N, Ishizuka S, Kiyoki M et al. Effects of 1,25-dihydroxyvitamin D3 on osteoblastic MC3T3¨CE1 cells. Endocrinology 1986;118:940¨C947.# F0 g3 J, [" ~3 ^+ o( y, f
) Q  V7 }* F* H9 H; i: J1 Y/ d( ?
Chaudhry GR, Yao D, Smith A et al. Osteogenic cells derived from embryonic stem cells produced bone nodules in three-dimensional scaffolds. J Biomed Biotechnol 2004;2004:203¨C210.8 |7 \3 H. ?$ e0 z9 z' Y+ W

Bourne S, Polak JM, Hughes SP et al. Osteogenic differentiation of mouse embryonic stem cells: Differential gene expression analysis by cDNA microarray and purification of osteoblasts by cadherin-11 magnetically activated cell sorting. Tissue Eng 2004;10:796¨C806.

Shimko DA, Burks CA, Dee KC et al. Comparison of in vitro mineralization by murine embryonic and adult stem cells cultured in an osteogenic medium. Tissue Eng 2004;10:1386¨C1398.

Bielby RC, Boccaccini AR, Polak JM et al. In vitro differentiation and in vivo mineralization of osteogenic cells derived from human embryonic stem cells. Tissue Eng 2004;10:1518¨C1525.
: z1 x+ u. w# y9 s
Friedman MS, Long MW, Hankenson KD. Osteogenic differentiation of human mesenchymal stem cells is regulated by bone morphogenetic protein-6. J Cell Biochem 2006;98:538¨C554.
5 f7 S7 A- Z1 N! S4 R4 x# @) G
Yang M, Mailhot G, Birnbaum MJ et al. Expression of and role for ovarian cancer G-protein-coupled receptor 1 (OGR1) during osteoclastogenesis. J Biol Chem 2006;281:23598¨C23605.6 ]+ q. E7 c5 Y6 K5 _
# a4 L1 t9 ]1 o" m
Zou W, Amcheslavsky A, Takeshita S et al. TNF-alpha expression is transcriptionally regulated by RANK ligand. J Cell Physiol 2005;202:371¨C378.  x$ |7 |! i8 X' k) O- p

Zhu LL, Zaidi S, Moonga BS et al. RANK-L induces the expression of NFATc1, but not of NFkappaB subunits during osteoclast formation. Biochem Biophys Res Commun 2005;326:131¨C135.
3 b4 V% `! ~2 {6 M$ X7 ~3 u4 L
Barton BE, Mayer R. IL-3 induces differentiation of bone marrow precursor cells to osteoclast-like cells. J Immunol 1989;143:3211¨C3216.
* B8 x! B5 j9 B+ d% A3 P
Hattersley G, Chambers TJ. Calcitonin receptors as markers for osteoclastic differentiation: Correlation between generation of bone-resorptive cells and cells that express calcitonin receptors in mouse bone marrow cultures. Endocrinology 1989;125:1606¨C1612.

Sasaki T, Takahashi N, Higashi S et al. Multinucleated cells formed on calcified dentine from mouse bone marrow cells treated with 1 alpha,25-dihydroxyvitamin D3 have ruffled borders and resorb dentine. Anat Rec 1989;224:379¨C391.! @$ [. b3 m" o. {/ t

Takahashi N, Yamana H, Yoshiki S et al. Osteoclast-like cell formation and its regulation by osteotropic hormones in mouse bone marrow cultures. Endocrinology 1988;122:1373¨C1382.
9 O0 M9 |. q6 e0 m% N4 _3 K
Wei S, Kitaura H, Zhou P et al. IL-1 mediates TNF-induced osteoclastogenesis. J Clin Invest 2005;115:282¨C290.
  q$ V; z1 w4 q* M
Gan OI, Soueidan A, Castagne A et al. Rat long-term bone marrow culture as a model for transient production of multinucleated giant cells into suspension culture fraction and for steady mineralization process of adherent stromal cells. C R Acad Sci III 1994;317:324¨C331., n$ P% L- l" C. d- |" v' M
4 O# R: ]! v2 v7 v( A6 ?
MacDonald BR, Takahashi N, McManus LM et al. Formation of multinucleated cells that respond to osteotropic hormones in long term human bone marrow cultures. Endocrinology 1987;120:2326¨C2333.+ T+ b. C$ m) w1 d+ _

Thavarajah M, Evans DB, Kanis JA. 1,25(OH)2D3 induces differentiation of osteoclast-like cells from human bone marrow cultures. Biochem Biophys Res Commun 1991;176:1189¨C1195.
- w0 ?- \1 j( i$ l' Y( v3 a/ G( J
Komano Y, Nanki T, Hayashida K et al. Identification of a human peripheral blood monocyte subset that differentiates into osteoclasts. Arthritis Res Ther 2006;8:R152.

Flanagan AM, Horton MA, Dorey EL et al. An assessment of the ability of human bone marrow cultures to generate osteoclasts. Int J Exp Pathol 1992;73:387¨C401.

Brage M, Lie A, Ransjo M et al. Osteoclastogenesis is decreased by cysteine proteinase inhibitors. Bone 2004;34:412¨C424., C) R7 g, X: g2 O" L% L$ C! `

Fuller K, Murphy C, Kirstein B et al. TNFalpha potently activates osteoclasts, through a direct action independent of and strongly synergistic with RANKL. Endocrinology 2002;143:1108¨C1118.

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