Col10a1

Summary

Gene Symbol: Col10a1
Description: collagen, type X, alpha 1
Alias: Col10, Col10a-1, collagen alpha-1(X) chain, procollagen, type X, alpha 1
Species: mouse
Products:     Col10a1

Top Publications

  1. Long F, Schipani E, Asahara H, Kronenberg H, Montminy M. The CREB family of activators is required for endochondral bone development. Development. 2001;128:541-50 pubmed
    ..These results demonstrate the presence of a distinct signaling pathway in developing bone that potentiates Ihh signaling and regulates chondrocyte proliferation, at least in part, via the CREB family of activators. ..
  2. Tavella S, Biticchi R, Schito A, Minina E, Di Martino D, Pagano A, et al. Targeted expression of SHH affects chondrocyte differentiation, growth plate organization, and Sox9 expression. J Bone Miner Res. 2004;19:1678-88 pubmed
    ..Transgenic mice show that continuous expression of SHH in chondrocytes interferes with cell differentiation and growth plate organization and induces high levels and diffuse expression of Sox9 in cartilaginous bones. ..
  3. Chung K, Jacenko O, Boyle P, Olsen B, Nishimura I. Craniofacial abnormalities in mice carrying a dominant interference mutation in type X collagen. Dev Dyn. 1997;208:544-52 pubmed
    ..The data suggested that the expression of the chick type X collagen transgene product was strongly associated with the craniofacial skeletal abnormalities that were distinct from other cartilage-related phenotypes. ..
  4. Takeda S, Bonnamy J, Owen M, Ducy P, Karsenty G. Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. Genes Dev. 2001;15:467-81 pubmed
    ..These results identify Cbfa1 as a hypertrophic chondrocyte differentiation factor and provide a genetic argument for a common regulation of osteoblast and chondrocyte differentiation mediated by Cbfa1. ..
  5. Mau E, Whetstone H, Yu C, Hopyan S, Wunder J, Alman B. PTHrP regulates growth plate chondrocyte differentiation and proliferation in a Gli3 dependent manner utilizing hedgehog ligand dependent and independent mechanisms. Dev Biol. 2007;305:28-39 pubmed
    ..These results show that PTHrP regulates growth plate chondrocyte proliferation and differentiation in part through the activity of Gli3, suggesting a crucial role for Gli3 in growth plate chondrocyte development. ..
  6. Vega R, Matsuda K, Oh J, Barbosa A, Yang X, Meadows E, et al. Histone deacetylase 4 controls chondrocyte hypertrophy during skeletogenesis. Cell. 2004;119:555-66 pubmed
    ..These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy. ..
  7. Bialek P, Kern B, Yang X, Schrock M, Sosic D, Hong N, et al. A twist code determines the onset of osteoblast differentiation. Dev Cell. 2004;6:423-35 pubmed
    ..In vivo mutagenesis confirms the antiosteogenic function of the Twist box. Thus, relief of inhibition by Twist proteins is a mandatory event precluding osteoblast differentiation. ..
  8. Boulet A, Capecchi M. Multiple roles of Hoxa11 and Hoxd11 in the formation of the mammalian forelimb zeugopod. Development. 2004;131:299-309 pubmed
    ..As a consequence, growth and maturation of these bones is highly disorganized, resulting in the creation of amorphous bony elements, rather than a normal radius and ulna. ..
  9. Liu Z, Xu J, Colvin J, Ornitz D. Coordination of chondrogenesis and osteogenesis by fibroblast growth factor 18. Genes Dev. 2002;16:859-69 pubmed
    ..Signaling to multiple FGFRs positions FGF18 to coordinate chondrogenesis in the growth plate with osteogenesis in cortical and trabecular bone. ..

More Information

Publications92

  1. Wai A, Ng L, Watanabe H, Yamada Y, Tam P, Cheah K. Disrupted expression of matrix genes in the growth plate of the mouse cartilage matrix deficiency (cmd) mutant. Dev Genet. 1998;22:349-58 pubmed
    ..of co-expression of genes encoding the glycoprotein link protein, proteoglycan syndecan 3, collagens alpha 1 (X) [Col10a1], alpha 2(XI) [Col11a2], and the alternative transcripts of alpha 1 (II) [Col2a1 type IIA form], and alpha 1 (IX) ..
  2. Aszodi A, Chan D, Hunziker E, Bateman J, Fassler R. Collagen II is essential for the removal of the notochord and the formation of intervertebral discs. J Cell Biol. 1998;143:1399-412 pubmed
  3. Robledo R, Rajan L, Li X, Lufkin T. The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev. 2002;16:1089-101 pubmed
    ..Furthermore, spatiotemporal-specific transgenic overexpression of Dlx5, in the apical ectodermal ridge of Dlx5/6 null mice can fully rescue Dlx/Dll function in limb outgrowth. ..
  4. Tsang K, Chan D, Cheslett D, Chan W, So C, Melhado I, et al. Surviving endoplasmic reticulum stress is coupled to altered chondrocyte differentiation and function. PLoS Biol. 2007;5:e44 pubmed
    ..In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded alpha1(X) chains accumulate in HCs and elicit ERSS...
  5. Karp S, Schipani E, St Jacques B, Hunzelman J, Kronenberg H, McMahon A. Indian hedgehog coordinates endochondral bone growth and morphogenesis via parathyroid hormone related-protein-dependent and -independent pathways. Development. 2000;127:543-8 pubmed
    ..This identifies Ihh as a coordinator of skeletal growth and morphogenesis, and refines the role of PTHrP in mediating a subset of Ihh's actions. ..
  6. Ikeda K, Tsukui T, Imazawa Y, Horie Inoue K, Inoue S. Conditional expression of constitutively active estrogen receptor ? in chondrocytes impairs longitudinal bone growth in mice. Biochem Biophys Res Commun. 2012;425:912-7 pubmed publisher
    ..These results suggest that ER? is a critical regulator of chondrocyte proliferation and maturation during skeletal development, mediating longitudinal bone growth in vivo. ..
  7. Iwata T, Chen L, Li C, Ovchinnikov D, Behringer R, Francomano C, et al. A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos. Hum Mol Genet. 2000;9:1603-13 pubmed
    ..This model was successfully crossed with a cartilage-specific CRE: transgenic strain, excluding the lung as the primary cause of lethality. ..
  8. Arikawa Hirasawa E, Watanabe H, Takami H, Hassell J, Yamada Y. Perlecan is essential for cartilage and cephalic development. Nat Genet. 1999;23:354-8 pubmed
    ..Our findings suggest that these molecules affect similar signalling pathways. ..
  9. Gebhard S, Poschl E, Riemer S, Bauer E, Hattori T, Eberspaecher H, et al. A highly conserved enhancer in mammalian type X collagen genes drives high levels of tissue-specific expression in hypertrophic cartilage in vitro and in vivo. Matrix Biol. 2004;23:309-22 pubmed
    ..Here we show that this enhancer is highly conserved also in the murine and bovine Col10a1 genes, but not found in the known promoter sequences of chicken Col10a1...
  10. Savontaus M, Metsaranta M, Vuorio E. Mutation in type II collagen gene disturbs spinal development and gene expression patterns in transgenic Del1 mice. Lab Invest. 1997;77:591-600 pubmed
    ..Many of these findings parallel those seen in human chondrodysplasias and help us to understand the pathogenetic mechanisms involved in these developmental abnormalities. ..
  11. Cameron T, Bell K, Tatarczuch L, Mackie E, Rajpar M, McDermott B, et al. Transcriptional profiling of chondrodysplasia growth plate cartilage reveals adaptive ER-stress networks that allow survival but disrupt hypertrophy. PLoS ONE. 2011;6:e24600 pubmed publisher
    ..Thus they provide important insights into ER stress signaling and its impact on cartilage pathophysiology...
  12. Smith N, Dong Y, Lian J, Pratap J, Kingsley P, Van Wijnen A, et al. Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development. J Cell Physiol. 2005;203:133-43 pubmed
  13. Colnot C, Lu C, Hu D, Helms J. Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol. 2004;269:55-69 pubmed
    ..Collectively, these studies clarify further the contributions of the cartilage, perichondrium, and vascular endothelium to long bone development. ..
  14. Garofalo S, Kliger Spatz M, Cooke J, Wolstin O, Lunstrum G, Moshkovitz S, et al. Skeletal dysplasia and defective chondrocyte differentiation by targeted overexpression of fibroblast growth factor 9 in transgenic mice. J Bone Miner Res. 1999;14:1909-15 pubmed
  15. Zhang P, Liegeois N, Wong C, Finegold M, Hou H, Thompson J, et al. Altered cell differentiation and proliferation in mice lacking p57KIP2 indicates a role in Beckwith-Wiedemann syndrome. Nature. 1997;387:151-8 pubmed
  16. Maes C, Stockmans I, Moermans K, Van Looveren R, Smets N, Carmeliet P, et al. Soluble VEGF isoforms are essential for establishing epiphyseal vascularization and regulating chondrocyte development and survival. J Clin Invest. 2004;113:188-99 pubmed
    ..These findings indicate that the insoluble VEGF(188) isoform is insufficient for establishing epiphyseal vascularization and regulating cartilage development during endochondral bone formation...
  17. Inada M, Yasui T, Nomura S, Miyake S, Deguchi K, Himeno M, et al. Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999;214:279-90 pubmed
    ..These findings demonstrate that Cbfa1 is an important factor for chondrocyte differentiation. ..
  18. Zheng Q, Zhou G, Morello R, Chen Y, Garcia Rojas X, Lee B. Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo. J Cell Biol. 2003;162:833-42 pubmed
    The alpha1(X) collagen gene (Col10a1) is the only known hypertrophic chondrocyte-specific molecular marker. Until recently, few transcriptional factors specifying its tissue-specific expression have been identified...
  19. Zelzer E, Glotzer D, Hartmann C, Thomas D, Fukai N, Soker S, et al. Tissue specific regulation of VEGF expression during bone development requires Cbfa1/Runx2. Mech Dev. 2001;106:97-106 pubmed
    ..The results demonstrate that Cbfa1 is a necessary component of a tissue specific genetic program that regulates VEGF during endochondral bone formation. ..
  20. Wuelling M, Kaiser F, Buelens L, Braunholz D, Shivdasani R, Depping R, et al. Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3. Dev Biol. 2009;328:40-53 pubmed publisher
    ..The differentiation of columnar and hypertrophic chondrocytes is supported by Trps1 independent of Gli3. Trps1 seems thus to organize chondrocyte differentiation interacting with different subsets of co-factors in distinct cell types. ..
  21. Koziel L, Kunath M, Kelly O, Vortkamp A. Ext1-dependent heparan sulfate regulates the range of Ihh signaling during endochondral ossification. Dev Cell. 2004;6:801-13 pubmed
    ..Finally, we propose that the development of exostoses in the human Hereditary Multiple Exostoses syndrome can be attributed to activation of Ihh signaling...
  22. Tsumaki N, Tanaka K, Arikawa Hirasawa E, Nakase T, Kimura T, Thomas J, et al. Role of CDMP-1 in skeletal morphogenesis: promotion of mesenchymal cell recruitment and chondrocyte differentiation. J Cell Biol. 1999;144:161-73 pubmed
    ..These results indicate that CDMP-1 antagonizes the ventralization signals from the notochord. Our study suggests a molecular mechanism by which CDMP-1 regulates the formation, growth, and differentiation of the skeletal elements. ..
  23. Inada M, Wang Y, Byrne M, Rahman M, Miyaura C, Lopez Otin C, et al. Critical roles for collagenase-3 (Mmp13) in development of growth plate cartilage and in endochondral ossification. Proc Natl Acad Sci U S A. 2004;101:17192-7 pubmed
    ..Cartilaginous growth plate abnormalities persisted in adult mice and phenocopied defects observed in human hereditary chondrodysplasias. Our findings demonstrate a unique role of Mmp13 in skeletal development. ..
  24. Ikegami D, Akiyama H, Suzuki A, Nakamura T, Nakano T, Yoshikawa H, et al. Sox9 sustains chondrocyte survival and hypertrophy in part through Pik3ca-Akt pathways. Development. 2011;138:1507-19 pubmed publisher
    ..Inactivation of Sox9 in the last few cell layers resulted in the absence of Col10a1 expression, suggesting that continued expression of Sox9 just prior to hypertrophy is necessary for chondrocyte ..
  25. Akiyama H, Lyons J, Mori Akiyama Y, Yang X, Zhang R, Zhang Z, et al. Interactions between Sox9 and beta-catenin control chondrocyte differentiation. Genes Dev. 2004;18:1072-87 pubmed
    ..Our results strongly suggest that chondrogenesis is controlled by interactions between Sox9 and the Wnt/beta-catenin signaling pathway. ..
  26. Long F, Chung U, Ohba S, McMahon J, Kronenberg H, McMahon A. Ihh signaling is directly required for the osteoblast lineage in the endochondral skeleton. Development. 2004;131:1309-18 pubmed
    ..We suggest that Ihh acts in vivo on a potential progenitor cell to promote osteoblast and prevent chondrocyte differentiation. ..
  27. Kong R, Kwan K, Lau E, Thomas J, Boot Handford R, Grant M, et al. Intron-exon structure, alternative use of promoter and expression of the mouse collagen X gene, Col10a-1. Eur J Biochem. 1993;213:99-111 pubmed
    ..In agreement with the generally accepted association of type-X collagen with endochondral ossification, in situ hybridization analyses indicate that Col10a-1 mRNA are restricted to the hypertrophic regions of growth cartilage. ..
  28. Yang Y, Topol L, Lee H, Wu J. Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development. 2003;130:1003-15 pubmed
    ..Our data indicate that Wnt5a and Wnt5b control the pace of transitions between different chondrocyte zones. ..
  29. Maes C, Goossens S, Bartunkova S, Drogat B, Coenegrachts L, Stockmans I, et al. Increased skeletal VEGF enhances beta-catenin activity and results in excessively ossified bones. EMBO J. 2010;29:424-41 pubmed publisher
    ..Moreover, the finding that VEGF can modulate beta-catenin activity may have widespread physiological and clinical ramifications. ..
  30. Purcell P, Joo B, Hu J, Tran P, Calicchio M, O Connell D, et al. Temporomandibular joint formation requires two distinct hedgehog-dependent steps. Proc Natl Acad Sci U S A. 2009;106:18297-302 pubmed publisher
    ..Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ. ..
  31. Tsumaki N, Nakase T, Miyaji T, Kakiuchi M, Kimura T, Ochi T, et al. Bone morphogenetic protein signals are required for cartilage formation and differently regulate joint development during skeletogenesis. J Bone Miner Res. 2002;17:898-906 pubmed
    ..These conclusions may account for the reason why multiple BMPs are coexpressed in cartilage. ..
  32. Maes C, Carmeliet P, Moermans K, Stockmans I, Smets N, Collen D, et al. Impaired angiogenesis and endochondral bone formation in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188. Mech Dev. 2002;111:61-73 pubmed
  33. Bandyopadhyay A, Tsuji K, Cox K, Harfe B, Rosen V, Tabin C. Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS Genet. 2006;2:e216 pubmed
    ..In contrast, we find that the loss of both BMP2 and BMP4 results in a severe impairment of osteogenesis. ..
  34. Gress C, Jacenko O. Growth plate compressions and altered hematopoiesis in collagen X null mice. J Cell Biol. 2000;149:983-93 pubmed
  35. Jacob A, Smith C, Partanen J, Ornitz D. Fibroblast growth factor receptor 1 signaling in the osteo-chondrogenic cell lineage regulates sequential steps of osteoblast maturation. Dev Biol. 2006;296:315-28 pubmed
    ..These data demonstrate that signaling through FGFR1 in osteoblasts is necessary to maintain the balance between bone formation and remodeling through a direct effect on osteoblast maturation. ..
  36. Dy P, Wang W, Bhattaram P, Wang Q, Wang L, Ballock R, et al. Sox9 directs hypertrophic maturation and blocks osteoblast differentiation of growth plate chondrocytes. Dev Cell. 2012;22:597-609 pubmed publisher
    ..hypertrophic chondrocytes, where it contributes with Mef2c to directly activate the major marker of these cells, Col10a1. These findings thus reveal that Sox9 remains a central determinant of the lineage fate and multistep ..
  37. Mak K, Kronenberg H, Chuang P, Mackem S, Yang Y. Indian hedgehog signals independently of PTHrP to promote chondrocyte hypertrophy. Development. 2008;135:1947-56 pubmed publisher
    ..In addition, we found that bone morphogenetic protein (Bmp) and Wnt/beta-catenin signaling in the cartilage may both mediate the effect of upregulated Ihh signaling in promoting chondrocyte hypertrophy. ..
  38. Lu J, Lian G, Lenkinski R, De Grand A, Vaid R, Bryce T, et al. Filamin B mutations cause chondrocyte defects in skeletal development. Hum Mol Genet. 2007;16:1661-75 pubmed
    ..These data suggest that disruption of the ECM-beta1-integrin-Flnb pathway contributes to defects in vertebral and distal limb development, similar to those seen in the human autosomal recessive SCT due to Flnb mutations. ..
  39. Plumb D, Dhir V, Mironov A, Ferrara L, Poulsom R, Kadler K, et al. Collagen XXVII is developmentally regulated and forms thin fibrillar structures distinct from those of classical vertebrate fibrillar collagens. J Biol Chem. 2007;282:12791-5 pubmed
    ..The transient nature of its expression and unusual fibrillar structure suggest that collagen XXVII plays a developmental role distinct from those of the classical fibrillar collagens. ..
  40. Guo X, Day T, Jiang X, Garrett Beal L, Topol L, Yang Y. Wnt/beta-catenin signaling is sufficient and necessary for synovial joint formation. Genes Dev. 2004;18:2404-17 pubmed
    ..Wnt4, Wnt14, and Wnt16 may play redundant roles in synovial joint induction by signaling through the beta-catenin-mediated canonical Wnt pathway. ..
  41. Smits P, Dy P, Mitra S, Lefebvre V. Sox5 and Sox6 are needed to develop and maintain source, columnar, and hypertrophic chondrocytes in the cartilage growth plate. J Cell Biol. 2004;164:747-58 pubmed
    ..In conclusion, Sox5 and Sox6 are needed for the establishment of multilayered growth plates, and thereby for proper and timely development of endochondral bones. ..
  42. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng J, Behringer R, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002;108:17-29 pubmed
    ..Thus, Osx acts downstream of Runx2/Cbfa1. Because Osx null preosteoblasts express typical chondrocyte marker genes, we propose that Runx2/Cbfa1-expressing preosteoblasts are still bipotential cells. ..
  43. Kim I, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80:159-70 pubmed
    ..Our studies identify Cbfa1 as a major positive regulator of chondrocyte differentiation. ..
  44. Bendall A, Hu G, Levi G, Abate Shen C. Dlx5 regulates chondrocyte differentiation at multiple stages. Int J Dev Biol. 2003;47:335-44 pubmed
  45. Jacenko O, Chan D, Franklin A, Ito S, Underhill C, Bateman J, et al. A dominant interference collagen X mutation disrupts hypertrophic chondrocyte pericellular matrix and glycosaminoglycan and proteoglycan distribution in transgenic mice. Am J Pathol. 2001;159:2257-69 pubmed
    ..A provocative hypothesis links the disruption of the collagen X pericellular network and GAG/PG decompartmentalization to the potential locus for hematopoietic failure in the collagen X mice. ..
  46. Smits P, Li P, Mandel J, Zhang Z, Deng J, Behringer R, et al. The transcription factors L-Sox5 and Sox6 are essential for cartilage formation. Dev Cell. 2001;1:277-90 pubmed
    ..L-Sox5 and Sox6 are thus redundant, potent enhancers of chondroblast functions, thereby essential for endochondral skeleton formation. ..
  47. Iwasaki M, Le A, Helms J. Expression of indian hedgehog, bone morphogenetic protein 6 and gli during skeletal morphogenesis. Mech Dev. 1997;69:197-202 pubmed
    ..Collectively our findings suggest that ihh participates in, but is not required for chondrocyte hypertrophy. ..
  48. Lefebvre V, Li P, de Crombrugghe B. A new long form of Sox5 (L-Sox5), Sox6 and Sox9 are coexpressed in chondrogenesis and cooperatively activate the type II collagen gene. EMBO J. 1998;17:5718-33 pubmed
    ..Our data suggest that L-Sox5/Sox6 and Sox9, which belong to two different classes of Sox transcription factors, cooperate with each other in expression of Col2a1 and possibly other genes of the chondrocytic program. ..
  49. Baffi M, Slattery E, Sohn P, Moses H, Chytil A, Serra R. Conditional deletion of the TGF-beta type II receptor in Col2a expressing cells results in defects in the axial skeleton without alterations in chondrocyte differentiation or embryonic development of long bones. Dev Biol. 2004;276:124-42 pubmed
    ..The data provide information regarding mechanisms of skeletal development and suggest that TGF-beta signaling is a critical component...
  50. Grashoff C, Aszodi A, Sakai T, Hunziker E, Fassler R. Integrin-linked kinase regulates chondrocyte shape and proliferation. EMBO Rep. 2003;4:432-8 pubmed
    ..These findings suggest that Ilk regulates actin reorganization in chondrocytes and modulates chondrocyte growth independently of phosphorylation of Pkb/Akt and GSK3-beta. ..
  51. Rosati R, Horan G, Pinero G, Garofalo S, Keene D, Horton W, et al. Normal long bone growth and development in type X collagen-null mice. Nat Genet. 1994;8:129-35 pubmed
    ..However, mice and humans with dominant acting type X collagen mutations have bone abnormalities, suggesting that only the presence of abnormal type X collagen can modify bone growth and development. ..
  52. Ijiri K, Zerbini L, Peng H, Correa R, Lu B, Walsh N, et al. A novel role for GADD45beta as a mediator of MMP-13 gene expression during chondrocyte terminal differentiation. J Biol Chem. 2005;280:38544-55 pubmed
    ..mouse embryos, defective mineralization and decreased bone growth accompanied deficient Mmp-13 and Col10a1 gene expression in the hypertrophic zone...
  53. Joeng K, Schumacher C, Zylstra Diegel C, Long F, Williams B. Lrp5 and Lrp6 redundantly control skeletal development in the mouse embryo. Dev Biol. 2011;359:222-9 pubmed publisher
    ..Thus, Lrp5 and 6 redundantly control embryonic skeletal development, likely through ?-catenin signaling. ..
  54. Kwan K, Pang M, Zhou S, Cowan S, Kong R, Pfordte T, et al. Abnormal compartmentalization of cartilage matrix components in mice lacking collagen X: implications for function. J Cell Biol. 1997;136:459-71 pubmed
    ..Mutations in the human collagen alpha1 (X) gene (COL10A1) in Schmid metaphyseal chondrodysplasia (SMCD) suggest a supportive role...
  55. Bi W, Huang W, Whitworth D, Deng J, Zhang Z, Behringer R, et al. Haploinsufficiency of Sox9 results in defective cartilage primordia and premature skeletal mineralization. Proc Natl Acad Sci U S A. 2001;98:6698-703 pubmed
    ..First, an early step presumably at the stage of mesenchymal condensation of cartilage primordia, and second, a later step preceding the transition of chondrocytes into hypertrophic chondrocytes...
  56. Joeng K, Long F. The Gli2 transcriptional activator is a crucial effector for Ihh signaling in osteoblast development and cartilage vascularization. Development. 2009;136:4177-85 pubmed publisher
    ..These results therefore provide direct genetic evidence that Gli2 and Gli3 collectively mediate all major aspects of Ihh function during endochondral skeletal development. ..
  57. Schipani E, Ryan H, Didrickson S, Kobayashi T, Knight M, Johnson R. Hypoxia in cartilage: HIF-1alpha is essential for chondrocyte growth arrest and survival. Genes Dev. 2001;15:2865-76 pubmed
  58. Chen X, Macica C, Nasiri A, Broadus A. Regulation of articular chondrocyte proliferation and differentiation by indian hedgehog and parathyroid hormone-related protein in mice. Arthritis Rheum. 2008;58:3788-97 pubmed publisher
    ..We conclude that the IHH-PTHrP axis participates in the maintenance of articular cartilage. Dysregulation of this system might contribute to the pathogenesis of arthritis. ..
  59. Patra D, Xing X, Davies S, Bryan J, Franz C, Hunziker E, et al. Site-1 protease is essential for endochondral bone formation in mice. J Cell Biol. 2007;179:687-700 pubmed
    ..These data suggest that S1P activity is necessary for a specialized ER stress response required by chondrocytes for the genesis of normal cartilage and thus endochondral ossification. ..
  60. Lanske B, Amling M, Neff L, Guiducci J, Baron R, Kronenberg H. Ablation of the PTHrP gene or the PTH/PTHrP receptor gene leads to distinct abnormalities in bone development. J Clin Invest. 1999;104:399-407 pubmed
    ..In the double-homozygous knockout mice, the delay in vascular invasion did not occur. Thus, PTHrP must slow vascular invasion by a mechanism independent of the PTH/PTHrP receptor. ..
  61. Long F, Zhang X, Karp S, Yang Y, McMahon A. Genetic manipulation of hedgehog signaling in the endochondral skeleton reveals a direct role in the regulation of chondrocyte proliferation. Development. 2001;128:5099-108 pubmed
    ..Taken together, the present study establishes Ihh as a key mitogen in the endochondral skeleton. ..
  62. Kobayashi T, Soegiarto D, Yang Y, Lanske B, Schipani E, McMahon A, et al. Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP. J Clin Invest. 2005;115:1734-42 pubmed
    ..These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP. ..
  63. Yoshida C, Furuichi T, Fujita T, Fukuyama R, Kanatani N, Kobayashi S, et al. Core-binding factor beta interacts with Runx2 and is required for skeletal development. Nat Genet. 2002;32:633-8 pubmed
    ..These findings indicate that Cbfbeta is required for the function of Runx2 in skeletal development. ..
  64. MacLean H, Guo J, Knight M, Zhang P, Cobrinik D, Kronenberg H. The cyclin-dependent kinase inhibitor p57(Kip2) mediates proliferative actions of PTHrP in chondrocytes. J Clin Invest. 2004;113:1334-43 pubmed
    ..These studies suggest that the effects of PTHrP on both the rate and extent of chondrocyte proliferation are mediated, at least in part, through suppression of p57 expression. ..
  65. Leung V, Gao B, Leung K, Melhado I, Wynn S, Au T, et al. SOX9 governs differentiation stage-specific gene expression in growth plate chondrocytes via direct concomitant transactivation and repression. PLoS Genet. 2011;7:e1002356 pubmed publisher
    ..The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of ..
  66. Nishioka K, Itoh S, Suemoto H, Kanno S, Gai Z, Kawakatsu M, et al. Trps1 deficiency enlarges the proliferative zone of growth plate cartilage by upregulation of Pthrp. Bone. 2008;43:64-71 pubmed publisher
    ..Taken together, these data provide the first genetic evidence that lack of Trps1 leads to overexpression of PTHrP, and that Trps1 is required to maintain the normal organization of chondrocytes in the growth plate. ..
  67. Koziel L, Wuelling M, Schneider S, Vortkamp A. Gli3 acts as a repressor downstream of Ihh in regulating two distinct steps of chondrocyte differentiation. Development. 2005;132:5249-60 pubmed
    ..Furthermore, by regulating distal chondrocyte differentiation, Gli3 seems to position the domain of PTHrP expression. ..
  68. Saito A, Hino S, Murakami T, Kanemoto S, Kondo S, Saitoh M, et al. Regulation of endoplasmic reticulum stress response by a BBF2H7-mediated Sec23a pathway is essential for chondrogenesis. Nat Cell Biol. 2009;11:1197-204 pubmed publisher
    ..Our findings provide a new link by which ER stress is converted to signalling for the activation of ER-to-Golgi trafficking. ..
  69. Blitz E, Viukov S, Sharir A, Shwartz Y, Galloway J, Pryce B, et al. Bone ridge patterning during musculoskeletal assembly is mediated through SCX regulation of Bmp4 at the tendon-skeleton junction. Dev Cell. 2009;17:861-73 pubmed publisher
    ..This study establishes a mechanistic basis for tendon-skeleton regulatory interactions during musculoskeletal assembly and bone secondary patterning. ..
  70. Hill T, Sp├Ąter D, Taketo M, Birchmeier W, Hartmann C. Canonical Wnt/beta-catenin signaling prevents osteoblasts from differentiating into chondrocytes. Dev Cell. 2005;8:727-38 pubmed
    ..Thus, canonical Wnt/beta-catenin signaling is essential for skeletal lineage differentiation, preventing transdifferentiation of osteoblastic cells into chondrocytes. ..
  71. Wang W, Lian N, Li L, Moss H, Wang W, Perrien D, et al. Atf4 regulates chondrocyte proliferation and differentiation during endochondral ossification by activating Ihh transcription. Development. 2009;136:4143-53 pubmed publisher
    ..chondrocyte marker genes, such as type II collagen (Col2a1), PTH/PTHrP receptor (Pth1r) and type X collagen (Col10a1), is normal...
  72. Naski M, Colvin J, Coffin J, Ornitz D. Repression of hedgehog signaling and BMP4 expression in growth plate cartilage by fibroblast growth factor receptor 3. Development. 1998;125:4977-88 pubmed
  73. Chung U, Lanske B, Lee K, Li E, Kronenberg H. The parathyroid hormone/parathyroid hormone-related peptide receptor coordinates endochondral bone development by directly controlling chondrocyte differentiation. Proc Natl Acad Sci U S A. 1998;95:13030-5 pubmed
    ..Thus, the PTH/PTHrP receptor directly controls the pace and synchrony of chondrocyte differentiation and thereby coordinates development of the growth plate and adjacent bone. ..
  74. Hu H, Hilton M, Tu X, Yu K, Ornitz D, Long F. Sequential roles of Hedgehog and Wnt signaling in osteoblast development. Development. 2005;132:49-60 pubmed
    ..Finally Wnt7b is identified as a potential endogenous ligand regulating osteogenesis. These data support a model that integrates Hh and Wnt signaling in the regulation of osteoblast development. ..
  75. Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, et al. Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development. Nat Med. 2010;16:678-86 pubmed publisher
    ..followed by cartilage matrix degradation and vascular invasion, characterized by expression of type X collagen (COL10A1), matrix metalloproteinase-13 (MMP-13) and vascular endothelial growth factor (VEGF), respectively, are central ..
  76. Tu X, Joeng K, Nakayama K, Nakayama K, Rajagopal J, Carroll T, et al. Noncanonical Wnt signaling through G protein-linked PKCdelta activation promotes bone formation. Dev Cell. 2007;12:113-27 pubmed
    ..Together, these results reveal a Wnt-dependent osteogenic mechanism, and they provide a potential target pathway for designing therapeutics to promote bone formation. ..
  77. Rajpar M, McDermott B, Kung L, Eardley R, Knowles L, Heeran M, et al. Targeted induction of endoplasmic reticulum stress induces cartilage pathology. PLoS Genet. 2009;5:e1000691 pubmed publisher
    ..We generated a knock-in mouse model of an MCDS-causing mutation (COL10A1 p.Asn617Lys) to investigate pathogenic mechanisms linking genotype and phenotype...
  78. Barbieri O, Astigiano S, Morini M, Tavella S, Schito A, Corsi A, et al. Depletion of cartilage collagen fibrils in mice carrying a dominant negative Col2a1 transgene affects chondrocyte differentiation. Am J Physiol Cell Physiol. 2003;285:C1504-12 pubmed
    ..Indian hedgehog (Ihh), runx2, cyclin-dependent kinase inhibitor P21CIP/WAF (Cdkn1a), and collagen type X (Col10a1), suggesting that a defective extracellular matrix (ECM) depleted of collagen fibrils affects chondrocytes ..
  79. Zhang R, Murakami S, Coustry F, Wang Y, de Crombrugghe B. Constitutive activation of MKK6 in chondrocytes of transgenic mice inhibits proliferation and delays endochondral bone formation. Proc Natl Acad Sci U S A. 2006;103:365-70 pubmed
    ..Therefore, our study provides in vivo evidence for the role of p38 in endochondral ossification and suggests that Sox9 is a likely downstream target of the p38 MAPK pathway. ..
  80. Hilton M, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, et al. Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med. 2008;14:306-14 pubmed publisher
    ..Thus, mesenchymal progenitors may be expanded in vitro by activating the Notch pathway, whereas bone formation in vivo may be enhanced by transiently suppressing this pathway. ..
  81. Yoon B, Pogue R, Ovchinnikov D, Yoshii I, Mishina Y, Behringer R, et al. BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways. Development. 2006;133:4667-78 pubmed
    ..These results provide a genetic in vivo demonstration that the progression of chondrocytes through the growth plate is controlled by antagonistic BMP and FGF signaling pathways. ..
  82. Sweeney E, Campbell M, Watkins K, Hunter C, Jacenko O. Altered endochondral ossification in collagen X mouse models leads to impaired immune responses. Dev Dyn. 2008;237:2693-704 pubmed publisher
    ..These data link the disruption of collagen X function in the chondro-osseous junction to an altered hematopoietic stem cell niche in the marrow, resulting in impaired immune function. ..
  83. Rossi F, MacLean H, Yuan W, Francis R, Semenova E, Lin C, et al. p107 and p130 Coordinately regulate proliferation, Cbfa1 expression, and hypertrophic differentiation during endochondral bone development. Dev Biol. 2002;247:271-85 pubmed
    ..The results suggest that Cbfa1 links a p107- and p130-mediated cell cycle arrest to chondrocyte terminal differentiation. ..