顎関節の成長と生涯にわたる構造維持を支える仕組みを解明 －神経栄養因子受容体p75NTRが軟骨細胞の生存・分化と 力学的負荷への適応を制御－

2026-10-27 東京科学大学

図1. ヒト顎関節の生涯にわたる変化と機能

＜関連情報＞

• https://www.isct.ac.jp/ja/news/75eyjpb5z3yv
• https://www.science.org/doi/10.1126/sciadv.aef7786

p75 NTRは、顎関節の発達と恒常性を維持するために、軟骨形成と機械的適応を調整する p75NTR orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis

Chiho Kadota-Watanabe, Jinsook Suh, Eric Yin, Byron Zhao, Jey Kim, Yan Zhang, In-Won Chang, Sowmya Ramesh, Yuna Lee, […] , and Christine Hong
Science Advances  Published:21 Oct 2026
DOI:https://doi.org/10.1126/sciadv.aef7786

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.