p75 NTR orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis
Year: 2026
Type: article
Abstract: The temporomandibular joint (TMJ) is essential for oral functions such as chewing, speaking, and swallowing. Temporomandibular disorders that impair these functions notably reduce patients’ quality of life, and few therapeutic strategies are available to ameliorate these conditions. Here, we identify the neurotrophin receptor (p75 NTR ) as a central regulator of mandibular condylar cartilage development, mechanoadaptation, and homeostasis. p75 NTR loss causes condylar and disc hypoplasia, reduced chondrocyte number, impaired load-induced anabolism, and accelerated degeneration. Conditional deletion experiments demonstrate chondrocyte-autonomous requirements for the brain-derived neurotrophic factor (BDNF)–p75 NTR axis, which activates phosphoinositide 3-kinase AKT serine/threonine kinase and p38 mitogen-activated protein kinase signaling to promote proliferation and chondrogenic differentiation while restraining apoptosis. Degenerative human condyles exhibit reduced p75 NTR expression levels. Together, these data establish p75 NTR as a molecular hub integrating neurotrophic and mechanical cues to preserve postnatal TMJ architecture and highlight the BDNF-p75 NTR axis as a potential therapeutic target.
Source: Science Advances
Authors: Chiho Kadota-Watanabe, Jinsook Suh, Eric Yin, Byron Zhao, Jey Kim, Yan Zhang, In-Won Chang, Sowmya Ramesh, Yuna Lee, Joshua Chen, Maulik Ahuja, Sara Jahangiri, Isabelle Lao-Ngo, Ursula Eisinger, Kate Lindsey, Haihui Zhang, Fatemeh Momen-Heravi, Juan Du, James M. Gardner, Rebeka Silva, Sumit Yadav, Chelsea S. Bahney, Aaron W. James, Reuben H. Kim, Ophir D. Klein, Christine Hong
Institutions: University of California, San Francisco, Institute of Science Tokyo, University of California, Los Angeles, Johns Hopkins University, UCSF Helen Diller Family Comprehensive Cancer Center, University of California San Francisco Medical Center, University of Nebraska Medical Center, Steadman Philippon Research Institute, Cedars-Sinai Medical Center, University of Washington
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,500
OpenAlex ID: W7223107283