Abstract
The bone morphogenetic protein 5 (BMP5) participates in skeletal development but its direct effects on the function of growth plate chondrocytes during chondrogenesis have not been explored. We have investigated the signaling pathways activated by BMP5 and its effect on chondrogenic differentiation in the ATDC5 growth plate chondrocyte model. BMP5 transiently activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase signaling after 10 days of differentiation; sustained Smad and p38 MAPK signaling were seen after 15 days differentiation. All three pathways were activated by BMP5 in human adult articular chondrocytes. BMP5 alone and in combination with the chondrogenic enhancer, insulin, induced proteoglycan synthesis, aggrecan core protein 1 expression, and alkaline phosphatase activity. Upregulation of hypertrophic markers parathyroid receptor 1 and collagen type X alpha 1 occurred in BMP5-treated ATDC5 cultures. BMP5 is clearly chondrogenic and exhibits stage-specific regulation of multiple signaling pathways in this growth plate model. In particular, BMP5 accelerates expression of hypertrophy markers which is of relevance in both development and diseases such as osteoarthritis.
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Acknowledgments
The authors would like to gratefully acknowledge Dr Jai Jun Choung, Dr Yun Zhang and Dr Zhidao Xia for the supply of reagents and cells.
Declaration of interest: This work was funded by Research into Ageing (grant number 257, SJBS and JL) and the Arthritis Research Campaign (Fellowship 16343 to PAH).
This work was also supported by the UK NIHR Musuculoskeletal Biomedical Research Unit a partnership between the Nuffield Orthopaedic Centre and the University of Oxford and the UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust.
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.