Differences in pathways contributing to thyroid hormone effects on postnatal cartilage calcification versus secondary ossification center development

  1. Gustavo A Gomez
  2. Patrick Aghajanian
  3. Sheila Pourteymoor
  4. Destiney Larkin
  5. Subburaman Mohan  Is a corresponding author
  1. Jerry L. Pettis Memorial VA Medical Center, United States
  2. 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

Article and author information

Author details

  1. Gustavo A Gomez

    Musculoskeletal Disease Centre, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, United States
    Competing interests
    No competing interests declared.
  2. Patrick Aghajanian

    Fulgent Genetics, El Monte, United States
    Competing interests
    Patrick Aghajanian, Patrick Aghajanian is affiliated with Fulgent Genetics. The author has no financial interests to declare..
  3. Sheila Pourteymoor

    Musculoskeletal Disease Centre, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, United States
    Competing interests
    No competing interests declared.
  4. Destiney Larkin

    Musculoskeletal Disease Centre, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, United States
    Competing interests
    No competing interests declared.
  5. Subburaman Mohan

    Musculoskeletal Disease Centre, Jerry L. Pettis Memorial VA Medical Center, Loma Linda, United States
    For correspondence
    Subburaman.Mohan@va.gov
    Competing interests
    Subburaman Mohan, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0063-986X

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.

Reviewing Editor

  1. Mone Zaidi, Icahn School of Medicine at Mount Sinai, United States

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.

Version history

  1. Received: December 30, 2021
  2. Preprint posted: January 7, 2022 (view preprint)
  3. Accepted: January 28, 2022
  4. Accepted Manuscript published: January 31, 2022 (version 1)
  5. Version of Record published: February 10, 2022 (version 2)

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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  1. Gustavo A Gomez
  2. Patrick Aghajanian
  3. Sheila Pourteymoor
  4. Destiney Larkin
  5. Subburaman Mohan
(2022)
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

Share this article

https://doi.org/10.7554/eLife.76730

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