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bioRxiv · 10.1101/2023.12.21.572937

Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints

Zhao, L.·Lai, Y.·Jiao, H.·Huang, J.
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Abstract

Osteoarthritis (OA) is a painful, incurable disease affecting over 500 million people. The need for relieving OA pain is paramount but inadequately addressed, partly due to limited understandings of how pain signaling regulates non-neural tissues. Here we report that nerve growth factor receptor (NGFR) is upregulated in skeletal cells during OA and plays an essential role in the remodeling and repair of osteoarthritic joints. Specifically, NGFR is expressed in osteochondral cells but not in skeletal progenitor cells and induced by TNF to attenuate NF-{kappa}B activation, maintaining proper BMP-SMAD1 signaling and suppressing RANKL expression. NGFR deficiency hyper-activates NF-{kappa}B in murine osteoarthritic joints, which impairs bone formation and enhances bone resorption as exemplified by a reduction in subchondral bone and osteophytes. In human OA cartilage, NGFR is also negatively associated with NF-{kappa}B activation. Together, this study uncovers a role of NGFR in limiting inflammation for repair of diseased skeletal tissues.

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Zhao, L., Lai, Y., Jiao, H., Huang, J.. 2023-12-22. Nerve Growth Factor Receptor Limits Inflammation to Promote Remodeling and Repair of Osteoarthritic Joints. https://doi.org/10.1101/2023.12.21.572937

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