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

2021 ◽  
pp. 101020
Author(s):  
Asra Almubarak ◽  
Rotem Lavy ◽  
Nikola Srnic ◽  
Yawen Hu ◽  
Devi Priyanka Maripuri ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Chondroprogenitor Cells

scholarly journals Exogenous Application of Proteoglycan to the Cell Surface Microenvironment Facilitates to Chondrogenic Differentiation and Maintenance

2020 ◽  
Vol 21 (20) ◽  
pp. 7744
Author(s):  
Teruaki Masutani ◽  
Shuhei Yamada ◽  
Akira Hara ◽  
Tatsuji Takahashi ◽  
Paul G Green ◽  
...  
Keyword(s):  
Cell Surface ◽  
Tyrosine Kinases ◽  
Endochondral Ossification ◽  
Three Dimensional ◽  
Treatment Strategies ◽  
Dimensional Structure ◽  
Pathophysiological Mechanism ◽  
Nasal Cartilage ◽  
Chondroprogenitor Cells ◽  
Extracellular Matrix Components

Osteoarthritis (OA), a disease that greatly impacts quality of life, has increasing worldwide prevalence as the population ages. However, its pathogenic mechanisms have not been fully elucidated and current therapeutic treatment strategies are inadequate. In recent years, abnormal endochondral ossification in articular cartilage has received attention as a pathophysiological mechanism in OA. Cartilage is composed of abundant extracellular matrix components, which are involved in tissue maintenance and regeneration, but how these factors affect endochondral ossification is not clear. Here, we show that the application of aggrecan-type proteoglycan from salmon nasal cartilage (sPG) exhibited marked proliferative capacity through receptor tyrosine kinases in chondroprogenitor cells, and also exhibited differentiation and three-dimensional structure formation via phosphorylation of Insulin-like Growth Factor-1 Receptor and Growth Differentiation Factor 5 expression. Furthermore, sPG inhibited calcification via expression of Runx2 and Col10 (factors related to induction of calcification), while increasing Mgp, a mineralization inhibitory factor. As a result of analyzing the localization of sPG applied to the cells, it was localized on the surface of the cell membrane. In this study, we found that sPG, as a biomaterial, could regulate cell proliferation, differentiation and calcification inhibition by acting on the cell surface microenvironment. Therefore, sPG may be the foundation for a novel therapeutic approach for cartilage maintenance and for improved symptoms in OA.

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 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 Activation of β–catenin-LEF/TCF signal pathway in chondrocytes stimulates ectopic endochondral ossification

2003 ◽  
Vol 11 (1) ◽  
pp. 36-43 ◽  
Author(s):  
J. Kitagaki ◽  
M. Iwamoto ◽  
J.-G. Liu ◽  
Y. Tamamura ◽  
M. Pacifci ◽  
...  
Keyword(s):  
Endochondral Ossification ◽  
Signal Pathway

scholarly journals PP2A in LepR+ mesenchymal stem cells contributes to embryonic and postnatal endochondral ossification through Runx2 dephosphorylation

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Yu-Ting Yen ◽  
May Chien ◽  
Pei-Yi Wu ◽  
Shih-Chieh Hung
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Bone Density ◽  
Endochondral Ossification ◽  
Bone Growth ◽  
Leptin Receptor ◽  
Trabecular Bone Density ◽  
Mature Adipocyte ◽  
Ossification Centers

AbstractIt has not been well studied which cells and related mechanisms contribute to endochondral ossification. Here, we fate mapped the leptin receptor-expressing (LepR+) mesenchymal stem cells (MSCs) in different embryonic and adult extremities using Lepr-cre; tdTomato mice and investigated the underling mechanism using Lepr-cre; Ppp2r1afl/fl mice. Tomato+ cells appear in the primary and secondary ossification centers and express the hypertrophic markers. Ppp2r1a deletion in LepR+ MSCs reduces the expression of Runx2, Osterix, alkaline phosphatase, collagen X, and MMP13, but increases that of the mature adipocyte marker perilipin, thereby reducing trabecular bone density and enhancing fat content. Mechanistically, PP2A dephosphorylates Runx2 and BRD4, thereby playing a major role in positively and negatively regulating osteogenesis and adipogenesis, respectively. Our data identify LepR+ MSC as the cell origin of endochondral ossification during embryonic and postnatal bone growth and suggest that PP2A is a therapeutic target in the treatment of dysregulated bone formation.

TRPV2 is involved in induction of lubricin and suppression of ectopic endochondral ossification in articular joints

2021 ◽  
Author(s):  
Hideki Nakamoto ◽  
Yuki Katanosaka ◽  
Ryota Chijimatsu ◽  
Daisuke Mori ◽  
Fengjun Xuan ◽  
...  
Keyword(s):  
Endochondral Ossification

scholarly journals The Skull’s Girder: A Brief Review of the Cranial Base

2021 ◽  
Vol 9 (1) ◽  
pp. 3
Author(s):  
Shankar Rengasamy Venugopalan ◽  
Eric Van Otterloo
Keyword(s):  
Birth Defects ◽  
Vertebral Column ◽  
Endochondral Ossification ◽  
Cranial Base ◽  
Facial Skeleton ◽  
The Core ◽  
Skull Vault ◽  
Congenital Birth Defects ◽  
Intimate Association ◽  
The Brain

The cranial base is a multifunctional bony platform within the core of the cranium, spanning rostral to caudal ends. This structure provides support for the brain and skull vault above, serves as a link between the head and the vertebral column below, and seamlessly integrates with the facial skeleton at its rostral end. Unique from the majority of the cranial skeleton, the cranial base develops from a cartilage intermediate—the chondrocranium—through the process of endochondral ossification. Owing to the intimate association of the cranial base with nearly all aspects of the head, congenital birth defects impacting these structures often coincide with anomalies of the cranial base. Despite this critical importance, studies investigating the genetic control of cranial base development and associated disorders lags in comparison to other craniofacial structures. Here, we highlight and review developmental and genetic aspects of the cranial base, including its transition from cartilage to bone, dual embryological origins, and vignettes of transcription factors controlling its formation.

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