Osteocytes regulate bone anabolic response to mechanical loading in male mice via activation of integrin α5

Dezhi Zhao, Rui Hua, Manuel A. Riquelme, Hongyun Cheng, Teja Guda, Huiyun Xu, Sumin Gu, Jean X Jiang

Research output: Contribution to journalArticlepeer-review

Abstract

Physical mechanical stimulation can maintain and even increase bone mass. Here, we report an important role of osteocytic integrin α5 in regulating the anabolic response of bone to mechanical loading using an Itga5 conditional gene knockout (cKO) mouse model. Integrin α5 gene deletion increased apoptotic osteocytes and reduced cortical anabolic responses to tibial compression including decreased endosteal osteoblasts and bone formation, and increased endosteal osteoclasts and bone resorption, contributing to the decreased bone area fraction and biomechanical properties, leading to an enlarged bone marrow area in cKO mice. Similar disruption of anabolic responses to mechanical loading was also detected in cKO trabecular bone. Moreover, integrin α5 deficiency impeded load-induced Cx43 hemichannel opening, and production and release of PGE2, an anabolic factor, resulting in attenuated effects of the loading on catabolic sclerostin (SOST) reduction and anabolic β-catenin increase. Together, this study shows an indispensable role of integrin α5 in osteocytes in the anabolic action of mechanical loading on skeletal tissue through activation of hemichannels and PGE2-evoked gene expression. Integrin α5 could act as a potential new therapeutic target for bone loss, especially in the elderly population with impeded mechanical sensitivity.

Original languageEnglish (US)
Article number49
JournalBone Research
Volume10
Issue number1
DOIs
StatePublished - Dec 2022

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Histology
  • Physiology

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