Article record

p75NTR协调软骨生成与机械适应以维持颞下颌关节发育和稳态

p75NTR orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis.

基础研究鼻科IF 14.8Q1

文献信息

PMID	42905810
原文	在 PubMed 查看原文 ↗
发表日期	2026
作者	Chiho Kadota-Watanabe 查看其他 25 位作者 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
作者单位	Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA. 查看其他 11 条单位信息 Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan.；Orthopaedic Trauma Institute, University of California, San Francisco, San Francisco, CA, USA.；The Shapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA.；Department of Pathology, Johns Hopkins University, Baltimore, MD, USA.；Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.；Department of Surgery, UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, USA.；Oral and Maxillofacial Surgery, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA.；Department of Growth and Development, University of Nebraska Medical Center, Omaha, NE, USA.；Center for Regenerative Medicine, Steadman Philippon Research Institute, Vail, CO, USA.；Department of Pediatrics, Cedars-Sinai Guerin Children's, Los Angeles, CA, USA.；Department of Orthodontics, School of Dentistry, University of Washington, Seattle, WA, USA.
期刊	Science advances
SCI 分区	Q1
IF	14.8
研究类型	基础研究 · 基础／转化
所属专科	鼻科

中文摘要

颞下颌关节（TMJ）对咀嚼、言语和吞咽等口腔功能至关重要。损害这些功能的颞下颌关节紊乱会显著降低患者生活质量，而改善这些状况的治疗策略很少。在此，我们确定神经营养素受体（p75NTR）是下颌髁突软骨发育、机械适应和稳态的核心调节因子。p75NTR缺失导致髁突和关节盘发育不全、软骨细胞数量减少、负荷诱导的合成代谢受损以及退变加速。条件性敲除实验证明软骨细胞对脑源性神经营养因子（BDNF）-p75NTR轴存在自主性需求，该轴激活磷脂酰肌醇3-激酶AKT丝氨酸/苏氨酸激酶和p38丝裂原活化蛋白激酶信号通路，以促进增殖和软骨生成分化，同时抑制凋亡。退变的人类髁突表现出p75NTR表达水平降低。总之，这些数据确立p75NTR是整合神经营养和机械线索以维持出生后TMJ结构和稳态的分子枢纽，并突出BDNF-p75NTR轴作为潜在治疗靶点。

英文摘要

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 (p75NTR) as a central regulator of mandibular condylar cartilage development, mechanoadaptation, and homeostasis. p75NTR 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)-p75NTR 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 p75NTR expression levels. Together, these data establish p75NTR as a molecular hub integrating neurotrophic and mechanical cues to preserve postnatal TMJ architecture and highlight the BDNF-p75NTR axis as a potential therapeutic target.