Brd4 is required for chondrocyte differentiation and endochondral ossification

Bone ◽  
2021 ◽  
pp. 116234
Author(s):  
Christopher R. Paradise ◽  
M. Lizeth Galvan ◽  
Oksana Pichurin ◽  
Sofia Jerez ◽  
Eva Kubrova ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Chondrocyte Differentiation

scholarly journals Role of CDMP-1 in Skeletal Morphogenesis: Promotion of Mesenchymal Cell Recruitment and Chondrocyte Differentiation

1999 ◽  
Vol 144 (1) ◽  
pp. 161-173 ◽  
Author(s):  
Noriyuki Tsumaki ◽  
Kazuhiro Tanaka ◽  
Eri Arikawa-Hirasawa ◽  
Takanobu Nakase ◽  
Tomoatsu Kimura ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Mesenchymal Cell ◽  
Chondrocyte Differentiation ◽  
Cell Recruitment ◽  
Body Formation ◽  
Morphogenetic Protein ◽  
Chondroprogenitor Cells ◽  
Skeletal Formation ◽  
Targeted Expression

Cartilage provides the template for endochondral ossification and is crucial for determining the length and width of the skeleton. Transgenic mice with targeted expression of recombinant cartilage-derived morphogenetic protein-1 (CDMP-1), a member of the bone morphogenetic protein family, were created to investigate the role of CDMP-1 in skeletal formation. The mice exhibited chondrodysplasia with expanded cartilage, which consists of the enlarged hypertrophic zone and the reduced proliferating chondrocyte zone. Histologically, CDMP-1 increased the number of chondroprogenitor cells and accelerated chondrocyte differentiation to hypertrophy. Expression of CDMP-1 in the notochord inhibited vertebral body formation by blocking migration of sclerotome cells to the notochord. 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.

scholarly journals A Novel Cell Culture Model of Chondrocyte Differentiation During Mammalian Endochondral Ossification

2001 ◽  
Vol 16 (2) ◽  
pp. 309-318 ◽  
Author(s):  
J. O. P. Cheung ◽  
M. C. Hillarby ◽  
S. Ayad ◽  
J. A. Hoyland ◽  
C. J. P. Jones ◽  
...  
Keyword(s):  
Cell Culture ◽  
Endochondral Ossification ◽  
Chondrocyte Differentiation ◽  
Cell Culture Model ◽  
Culture Model

Leptin regulates chondrocyte differentiation and matrix maturation during endochondral ossification

Bone ◽  
2005 ◽  
Vol 37 (5) ◽  
pp. 607-621 ◽  
Author(s):  
Yuki Kishida ◽  
Makoto Hirao ◽  
Noriyuki Tamai ◽  
Akihide Nampei ◽  
Tetsuho Fujimoto ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Chondrocyte Differentiation ◽  
Matrix Maturation

scholarly journals Loss of Foxc1 and Foxc2 function in chondroprogenitor cells disrupts endochondral ossification

2021 ◽  
Author(s):  
Asra Almubarak ◽  
Rotem Lavy ◽  
Nikola Srnic ◽  
Yawen Hu ◽  
Devi P. Maripuri ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Growth Plate ◽  
Endochondral Ossification ◽  
Expression Patterns ◽  
Embryonic Stem ◽  
Chondrocyte Differentiation ◽  
Growth Plate Chondrocytes ◽  
Chondroprogenitor Cells

AbstractEndochondral ossification forms and grows the majority of the mammalian skeleton and is tightly controlled through gene regulatory networks. The forkhead box transcription factors Foxc1 and Foxc2 have been demonstrated to regulate aspects of osteoblast function in the formation of the skeleton but their roles in chondrocytes to control endochondral ossification are less clear. We demonstrate that Foxc1 expression is directly regulated by SOX9 activity, one of the earliest transcription factors to specify the chondrocyte lineages. Moreover we demonstrate that elevelated expression of Foxc1 promotes chondrocyte differentiation in mouse embryonic stem cells and loss of Foxc1 function inhibits chondrogenesis in vitro. Using chondrocyte-targeted deletion of Foxc1 and Foxc2 in mice, we reveal a role for these factors in chondrocyte differentiation in vivo. Loss of both Foxc1 and Foxc2 caused a general skeletal dysplasia predominantly affecting the vertebral column. The long bones of the limb were smaller and mineralization was reduced and organization of the growth plate was disrupted. In particular, the stacked columnar organization of the proliferative chondrocyte layer was reduced in size and cell proliferation in growth plate chondrocytes was reduced. Differential gene expression analysis indicated disrupted expression patterns in chondrogenesis and ossification genes throughout the entire process of endochondral ossification in Col2-cre;Foxc1Δ/Δ;Foxc2Δ/Δ embryos. Our results suggest that Foxc1 and Foxc2 are required for correct chondrocyte differentiation and function. Loss of both genes results in disorganization of the growth plate, reduced chondrocyte proliferation and delays in chondrocyte hypertrophy that prevents correct ossification of the endochondral skeleton.

scholarly journals Studies on the role of Dlx5 in regulation of chondrocyte differentiation during endochondral ossification in the developing mouse limb

2007 ◽  
Vol 49 (6) ◽  
pp. 515-521 ◽  
Author(s):  
Hsian‐Jean Chin ◽  
Melanie C. Fisher ◽  
Yingcui Li ◽  
Deborah Ferrari ◽  
Chi‐Kuang Leo Wang ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Chondrocyte Differentiation ◽  
Mouse Limb

scholarly journals Sox9 Family Members Negatively Regulate Maturation and Calcification of Chondrocytes through Up-Regulation of Parathyroid Hormone–related Protein

2009 ◽  
Vol 20 (21) ◽  
pp. 4541-4551 ◽  
Author(s):  
Katsuhiko Amano ◽  
Kenji Hata ◽  
Atsushi Sugita ◽  
Yoko Takigawa ◽  
Koichiro Ono ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Endochondral Ossification ◽  
Family Members ◽  
Chondrocyte Differentiation ◽  
Related Protein ◽  
Primary Chondrocytes ◽  
Chondrocyte Maturation ◽  
Parathyroid Hormone Related Protein ◽  
Pthrp Expression ◽  
Late Stages

Sox9 is a transcription factor that plays an essential role in chondrogenesis and has been proposed to inhibit the late stages of endochondral ossification. However, the molecular mechanisms underlying the regulation of chondrocyte maturation and calcification by Sox9 remain unknown. In this study, we attempted to clarify roles of Sox9 in the late stages of chondrocyte differentiation. We found that overexpression of Sox9 alone or Sox9 together with Sox5 and Sox6 (Sox5/6/9) inhibited the maturation and calcification of murine primary chondrocytes and up-regulated parathyroid hormone–related protein (PTHrP) expression in primary chondrocytes and the mesenchymal cell line C3H10T1/2. Sox5/6/9 stimulated the early stages of chondrocyte proliferation and development. In contrast, Sox5/6/9 inhibited maturation and calcification of chondrocytes in organ culture. The inhibitory effects of Sox5/6/9 were rescued by treating with anti-PTHrP antibody. Moreover, Sox5/6/9 bound to the promoter region of the PTHrP gene and up-regulated PTHrP gene promoter activity. Interestingly, we also found that the Sox9 family members functionally collaborated with Ihh/Gli2 signaling to regulate PTHrP expression and chondrocyte differentiation. Our results provide novel evidence that Sox9 family members mediate endochondral ossification by up-regulating PTHrP expression in association with Ihh/Gli2 signaling.

Effect of ascorbic acid and 1,25(OH)2D3 on bone cell metabolism in relation to the development of tibial dyschondroplasia.

1993 ◽  
Vol 1993 ◽  
pp. 230-230
Author(s):  
C. Farquharso ◽  
J.S. Rennie ◽  
N. Loveridge ◽  
C.C. Whitehead
Keyword(s):  
Ascorbic Acid ◽  
Endochondral Ossification ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Chondrocyte Differentiation ◽  
Fast Growing ◽  
Tibial Dyschondroplasia ◽  
Welfare Implications ◽  
Endogenous Synthesis

Tibial dyschondroplasia (TD) results from a defect in endochondral ossification and is characterised by an accumulation of avascular cartilage extending distally from the growth plate. The lesion develops in young fast growing birds (broilers and turkeys) and is thought to be a result of incomplete chondrocyte differentiation. This condition can result in deformed bones and lameness and has therefore many economic and welfare implications.Since its description 25 years ago, TD has been studied extensively. The majority of the research has focused on determining the role of nutrition in the aetiology of the disease but it has only recently been shown that this disorder can be completely prevented by supplementing the diet with 1,25(OH)2 D3 (Rennie et al., 1993).This may be related to the hormones ability to increase the rate of chondrocyte differentiation (Farquharson et al., 1993). Since ascorbic acid (AA) has been shown previously to stimulate the endogenous synthesis of 1,25(OH)2 D3 (Weiser et al. 1988), its effect on the development of TD in young fast growing broilers was investigated

TBX1 Regulates Chondrocyte Maturation in the Spheno-occipital Synchondrosis

2020 ◽  
Vol 99 (10) ◽  
pp. 1182-1191 ◽  
Author(s):  
N. Funato ◽  
D. Srivastava ◽  
S. Shibata ◽  
H. Yanagisawa
Keyword(s):  
Digeorge Syndrome ◽  
Endochondral Ossification ◽  
Transcriptional Activity ◽  
Ectopic Expression ◽  
Chondrocyte Differentiation ◽  
Craniofacial Skeleton ◽  
Chondrocyte Maturation ◽  
Expression Of Genes ◽  
Growth Center ◽  
Deficient Mice

The synchondrosis in the cranial base is an important growth center for the craniofacial region. Abnormalities in the synchondroses affect the development of adjacent regions, including the craniofacial skeleton. Here, we report that the transcription factor TBX1, the candidate gene for DiGeorge syndrome, is expressed in mesoderm-derived chondrocytes and plays an essential and specific role in spheno-occipital synchondrosis development by inhibiting the expression of genes involved in chondrocyte hypertrophy and osteogenesis. In Tbx1-deficient mice, the spheno-occipital synchondrosis was completely mineralized at birth. TBX1 interacts with RUNX2, a master molecule of osteoblastogenesis and a regulator of chondrocyte maturation, and suppresses its transcriptional activity. Indeed, deleting Tbx1 triggers accelerated mineralization due to accelerated chondrocyte differentiation, which is associated with ectopic expression of downstream targets of RUNX2 in the spheno-occipital synchondrosis. These findings reveal that TBX1 acts as a regulator of chondrocyte maturation and osteogenesis during the spheno-occipital synchondrosis development. Thus, the tight regulation of endochondral ossification by TBX1 is crucial for the normal progression of chondrocyte differentiation in the spheno-occipital synchondrosis.

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