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Inhibition of inflammatory osteoclasts accelerates callus remodeling in osteoporotic fractures by enhancing CGRP+TrkA+ signaling.
Shu, Yuexia; Tan, Zhenyu; Pan, Zhen; Chen, Yujie; Wang, Jielin; He, Jieming; Wang, Jia; Wang, Yuan.
Afiliación
  • Shu Y; Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Tan Z; Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai, China.
  • Pan Z; Department of Orthopedics, TongRen Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China.
  • Chen Y; Department of Pathology, Tongji Hospital, Tongji University, Shanghai, China.
  • Wang J; Laboratory of Key Technology and Materials in Minimally Invasive Spine Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • He J; Center for Spinal Minimally Invasive Research, Shanghai Jiao Tong University, Shanghai, China.
  • Wang J; Department of Orthopedics, TongRen Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai, China.
  • Wang Y; Department of Orthopedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
Cell Death Differ ; 2024 Sep 02.
Article en En | MEDLINE | ID: mdl-39223264
ABSTRACT
Impaired callus remodeling significantly contributes to the delayed healing of osteoporotic fractures; however, the underlying mechanisms remain unclear. Sensory neuronal signaling plays a crucial role in bone repair. In this study, we aimed to investigate the pathological mechanisms hindering bone remodeling in osteoporotic fractures, particularly focusing on the role of sensory neuronal signaling. We demonstrate that in ovariectomized (OVX) mice, the loss of CGRP+TrkA+ sensory neuronal signaling during callus remodeling correlates with increased Cx3cr1+iOCs expression within the bone callus. Conditional knockout of Cx3cr1+iOCs restored CGRP+TrkA+ sensory neuronal, enabling normal callus remodeling progression. Mechanistically, we further demonstrate that Cx3cr1+iOCs secrete Sema3A in the osteoporotic fracture repair microenvironment, inhibiting CGRP+TrkA+ sensory neurons' axonal regeneration and suppressing nerve-bone signaling exchange, thus hindering bone remodeling. Lastly, in human samples, we observed an association between the loss of CGRP+TrkA+ sensory neuronal signaling and increased expression of Cx3cr1+iOCs. In conclusion, enhancing CGRP+TrkA+ sensory nerve signaling by inhibiting Cx3cr1+iOCs activity presents a potential strategy for treating delayed healing in osteoporotic fractures. Inhibition of inflammatory osteoclasts enhances CGRP+TrkA+ signaling and accelerates callus remodeling in osteoporotic fractures.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Differ Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Death Differ Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido