Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development
- Jerry L. Pettis Memorial VA Medical Center, United States
- Fulgent Genetics, United States
Abstract
The proximal and distal femur epiphysis of mice are both weight bearing structures derived from chondrocytes but differ in development. Mineralization at the distal epiphysis occurs in an osteoblast rich secondary ossification center (SOC), while the chondrocytes of the proximal femur head (FH) in particular, are directly mineralized. Thyroid hormone (TH) plays important roles in distal knee SOC formation, but whether TH also affects proximal FH development remains unexplored. Here, we found that TH controls chondrocyte maturation and mineralization at the FH in vivo through studies in Thyroid stimulating hormone receptor (Tshr-/-) hypothyroid mice by X-ray, histology, transcriptional profiling, and immunofluorescence staining. Both in vivo, and in vitro studies conducted in ATDC5 chondrocyte progenitors concur that TH regulates expression of genes that modulate mineralization (Ibsp, Bglap2, Dmp1, Spp1, and Alpl). Our work also delineates differences in prominent transcription factor regulation of genes involved in the different mechanisms leading to proximal FH cartilage calcification and endochondral ossification at the distal femur. The information on the molecular pathways contributing to postnatal cartilage calcification can provide insights on therapeutic strategies to treat pathological calcification that occurs in soft tissues such as aorta, kidney, and articular cartilage.
Data availability
The numeral data used to generate figures were uploaded separately as: Figure 3 -Source Data 1-3; Figure 9 - Source Data 1-6; Figure 9- figure supplement 1- source data 1-4; Figure 9- figure supplement 2-source data 1; Figure 9- figure supplement 3- source data 1
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Funding
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR048139)
- Subburaman Mohan
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All procedures were approved by the Institutional Animal Care and Use Committees of the VA Loma Linda Healthcare System (Permit Number: 0029/204). Every effort was made to minimize animal suffering.
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development
eLife 11:e76730.
https://doi.org/10.7554/eLife.76730
