Thyroid Hormones Regulate Hypertrophic Chondrocyte Differentiation and Expression of Parathyroid Hormone-Related Peptide and Its Receptor During Endochondral Bone Formation

2000 ◽  
Vol 15 (12) ◽  
pp. 2431-2442 ◽  
Author(s):  
David A. Stevens ◽  
Robert P. Hasserjian ◽  
Helen Robson ◽  
Thomas Siebler ◽  
Stephen M. Shalet ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Formation ◽  
Thyroid Hormones ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Endochondral Bone ◽  
Related Peptide ◽  
Hypertrophic Chondrocyte ◽  
Parathyroid Hormone Related Peptide

scholarly journals Regulation of terminal hypertrophic chondrocyte differentiation in Prmt5 mutant mice modeling infantile idiopathic scoliosis

2019 ◽  
Author(s):  
Zhaoyang Liu ◽  
Janani Ramachandran ◽  
Steven A Vokes ◽  
Ryan S Gray
Keyword(s):  
Bone Formation ◽  
Idiopathic Scoliosis ◽  
Age Of Onset ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Respiratory Compromise ◽  
Endochondral Bone ◽  
Hypertrophic Chondrocyte ◽  
Infantile Idiopathic Scoliosis ◽  
Adult Spine

ABSTRACTIdiopathic scoliosis (IS) is the most common type of musculoskeletal defect effecting children and is classified by age of onset, location, and degree of spine curvature. Although rare, the onset of IS during infancy is the more severe and rapidly progressive form of the disease, leading to increased mortality due to significant respiratory compromise. The pathophysiology of IS, in particular for infantile IS, remain elusive. Here, we show that PRMT5 is critical for the regulation of terminal hypertrophic chondrocyte differentiation in the spine and models infantile IS in mouse. Conditional ablation of PRMT5 in osteochondral progenitors led to impaired terminal hypertrophic chondrocyte differentiation and asymmetric defects of endochondral bone formation in the perinatal spine. Analysis of several markers of endochondral ossification revealed increased COLX and Ihh expression and a dramatic reduction of Mmp13 and RUNX2 expression in the intervertebral disc and vertebral growth plate. Furthermore, we demonstrate that PRMT5 function in committed chondrogenic lineages is required for regulation of COLX expression in the adult spine. Together, our results establish PRMT5 as a critical regulator of hypertrophic chondrocyte differentiation and endochondral bone formation in spine development and maintenance.

scholarly journals Dmrt2 promotes transition of endochondral bone formation by linking Sox9 and Runx2

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Koichiro Ono ◽  
Kenji Hata ◽  
Eriko Nakamura ◽  
Shota Ishihara ◽  
Sachi Kobayashi ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Bone Formation ◽  
Skeletal Development ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Endochondral Bone ◽  
Chondrocyte Hypertrophy ◽  
Hypertrophic Chondrocyte ◽  
Delayed Initiation ◽  
Related Transcription Factor

AbstractEndochondral bone formation is fundamental for skeletal development. During this process, chondrocytes undergo multiple steps of differentiation and coordinated transition from a proliferating to a hypertrophic stage, which is critical to advance skeletal development. Here, we identified the transcription factor Dmrt2 (double-sex and mab-3 related transcription factor 2) as a Sox9-inducible gene that promotes chondrocyte hypertrophy in pre-hypertrophic chondrocytes. Epigenetic analysis further demonstrated that Sox9 regulates Dmrt2 expression through an active enhancer located 18 kb upstream of the Dmrt2 gene and that this enhancer’s chromatin status is progressively activated through chondrocyte differentiation. Dmrt2-knockout mice exhibited a dwarf phenotype with delayed initiation of chondrocyte hypertrophy. Dmrt2 augmented hypertrophic chondrocyte gene expression including Ihh through physical and functional interaction with Runx2. Furthermore, Dmrt2 deficiency reduced Runx2-dependent Ihh expression. Our findings suggest that Dmrt2 is critical for sequential chondrocyte differentiation during endochondral bone formation and coordinates the transcriptional network between Sox9 and Runx2.

scholarly journals Prolyl Hydroxylase Domain-Containing Protein 3 Gene Expression in Chondrocytes Is Not Essential for Bone Development in Mice

Cells ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 2200
Author(s):  
Weirong Xing ◽  
Sheila Pourteymoor ◽  
Gustavo A. Gomez ◽  
Yian Chen ◽  
Subburaman Mohan
Keyword(s):  
Gene Expression ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Bone Volume ◽  
Endochondral Bone Formation ◽  
Chondrocyte Differentiation ◽  
Trabecular Bone Volume ◽  
Endochondral Bone ◽  
Trabecular Bone Mass

We previously showed that conditional disruption of the Phd2 gene in chondrocytes led to a massive increase in long bone trabecular bone mass. Loss of Phd2 gene expression or inhibition of PHD2 activity by a specific inhibitor resulted in a several-fold compensatory increase in Phd3 expression in chondrocytes. To determine if expression of PHD3 plays a role in endochondral bone formation, we conditionally disrupted the Phd3 gene in chondrocytes by crossing Phd3 floxed (Phd3flox/flox) mice with Col2α1-Cre mice. Loss of Phd3 expression in the chondrocytes of Cre+; Phd3flox/flox conditional knockout (cKO) mice was confirmed by real time PCR. At 16 weeks of age, neither body weight nor body length was significantly different in the Phd3 cKO mice compared to Cre−; Phd3flox/flox wild-type (WT) mice. Areal BMD measurements of total body as well as femur, tibia, and lumbar skeletal sites were not significantly different between the cKO and WT mice at 16 weeks of age. Micro-CT measurements revealed significant gender differences in the trabecular bone volume adjusted for tissue volume at the secondary spongiosa of the femur and the tibia for both genotypes, but no genotype difference was found for any of the trabecular bone measurements of either the femur or the tibia. Trabecular bone volume of distal femur epiphysis was not different between cKO and WT mice. Histology analyses revealed Phd3 cKO mice exhibited a comparable chondrocyte differentiation and proliferation, as evidenced by no changes in cartilage thickness and area in the cKO mice as compared to WT littermates. Consistent with the in vivo data, lentiviral shRNA-mediated knockdown of Phd3 expression in chondrocytes did not affect the expression of markers of chondrocyte differentiation (Col2, Col10, Acan, Sox9). Our study found that Phd2 but not Phd3 expressed in chondrocytes regulates endochondral bone formation, and the compensatory increase in Phd3 expression in the chondrocytes of Phd2 cKO mice is not the cause for increased trabecular bone mass in Phd2 cKO mice.

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