Skip to main content
  • Poster presentation
  • Open access
  • Published:

Cartilage-specific deletion of prar-gamma in mice results in early endochondral ossification defects and accelerated aging-dependent development of osteoarthritis


Long bones develop through a strict coordinated process of endochondral ossification within the growth plate resulting in the replacement of cartilage by bone and defect in this coordinated process may result in skeletal abnormalities such as dwarfism, kyposis and also age-related defects such as osteoarthritis (OA). PPARγ, a transcription factor, plays a key role in lipid homeostasis but its in vivo role in cartilage/bone development is unknown. Therefore, we determined the specific in vivo role of PPARγ in endochondral bone ossification, cartilage/bone development and in OA using cartilage-specific PPARγ knockout (KO) mice.

Materials and methods

Cartilage-specific PPARγ KO mice were generated using LoxP/Cre system. Histomorphometric/immunohistochemical analysis was performed to account for ossification patterns, chondrocyte proliferation, differentiation, hypertrophy, skeletal organization, bone density, calcium deposition and mouse OA phenotypic changes during aging using OARSI scoring. Real-Time PCR and western blotting was performed to determine the expression of key markers involved in endochondral ossification and cartilage degradation.


Histomorphometric analyses of embryonic and adult mutant mice demonstrate reduced long bone growth, calcium deposition, bone density, vascularity as well as delayed primary and secondary ossification. Mutant growth plates are disorganized with reduced cellularity, proliferation, differentiation, hypertrophy and loss of columnar organization. Isolated chondrocytes and cartilage explants from E16.5 and 3 weeks old mutant mice further show decreased expression of ECM production products, aggrecan and collagen II, and increased expression of catabolic enzyme, MMP-13. Furthermore, aged mutant mice exhibit accelerated OA-like phenotypes associated with enhanced cartilage degradation, synovial inflammation, and increased expression of MMP-13, and MMP-generated aggrecan and collagen II neoepitopes. Subsequently, we show that loss of PPARγ and subsequent downstream alterations in phosphatase and tensin homolog on chromosome ten (PTEN)/Akt pathway contribute towards increased expression of OA catabolic and inflammatory markers, thus enabling the articular cartilage of PPARγ-deficient mice to be more susceptible to degradation during aging.


For the first time, we demonstrate that loss of PPARγ in the cartilage results in endochondral bone defects and subsequently accelerated OA in mice. PPARγ is essential for normal development of cartilage and bone.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article

Monemdjou, R., Vasheghani, F., Fahmi, H. et al. Cartilage-specific deletion of prar-gamma in mice results in early endochondral ossification defects and accelerated aging-dependent development of osteoarthritis. Arthritis Res Ther 14 (Suppl 1), P31 (2012).

Download citation

  • Published:

  • DOI: