首页|Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption

Mechanical protein polycystin-1 directly regulates osteoclastogenesis and bone resorption

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Mechanical loading is required for bone homeostasis,but the underlying mechanism is still unclear.Our previous studies revealed that the mechanical protein polycystin-1(PC1,encoded by Pkd1)is critical for bone formation.However,the role of PC1 in bone resorption is unknown.Here,we found that PC1 directly regulates osteoclastogenesis and bone resorption.The conditional deletion of Pkd1 in the osteo-clast lineage resulted in a reduced number of osteoclasts,decreased bone resorption,and increased bone mass.A cohort study of 32,500 patients further revealed that autosomal dominant polycystic kidney dis-ease,which is mainly caused by loss-of-function mutation of the PKD1 gene,is associated with a lower risk of hip fracture than those with other chronic kidney diseases.Moreover,mice with osteoclast-specific knockout of Pkd1 showed complete resistance to unloading-induced bone loss.A mechanistic study revealed that PC1 facilitated TAZ nuclear translocation via the C-terminal tail-TAZ complex and that conditional deletion of Taz in the osteoclast lineage resulted in reduced osteoclastogenesis and increased bone mass.Pharmacological regulation of the PC1-TAZ axis alleviated unloading-and estrogen deficiency-induced bone loss.Thus,the PC1-TAZ axis may be a potential therapeutic target for osteoclast-related osteoporosis.

Polycystin1OsteoclastogenesisBone resorptionMechanical stress

Mei Huang、Jingxuan Zhou、Xiaoxiao Li、Ran Liu、Yangzi Jiang、Kaixuan Chen、Yurui Jiao、Xin Yin、Ling Liu、Yuchen Sun、Weishan Wang、Ye Xiao、Tian Su、Qi Guo、Yan Huang、Mi Yang、Jie Wei、L.Darryl Quarles、Zhousheng Xiao、Chao Zeng、Xianghang Luo、Guanghua Lei、Changjun Li

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Department of Endocrinology,Endocrinology Research Center,Xiangya Hospital,Central South University,Changsha 410008,China

Hunan Key Laboratory of Joint Degeneration and Injury,Changsha 410008,China

Key Laboratory of Aging-related Bone and Joint Diseases Prevention and Treatment,Ministry of Education,Xiangya Hospital,Central South University,Changsha 410008,China

School of Biomedical Sciences,Institute for Tissue Engineering and Regenerative Medicine,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong 999077,China

Key Laboratory for Regenerative Medicine,Ministry of Education,School of Biomedical Sciences,Faculty of Medicine,The Chinese University of Hong Kong,Hong Kong 999077,China

Center for Neuromusculoskeletal Restorative Medicine(CNRM),The Chinese University of Hong Kong,Hong Kong 999077,China

Department of Orthopaedics,The First Affiliated Hospital of Shihezi University,Shihezi 832061,China

Department of Orthopaedics,Xiangya Hospital,Central South University,Changsha 410008,China

Department of Epidemiology and Health Statistics,Xiangya School of Public Health,Central South University,Changsha 410008,China

Department of Medicine,University of Tennessee Health Science Center,Memphis 38163,USA

National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Central South University,Changsha 410008,China

Laboratory Animal Center,Xiangya Hospital,Central South University,Changsha 410008,China

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National Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Key Research and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNSFC/RGC Joint Research SchemeResearch Grants Council(UGC)of the Hong Kong Special Administrative RegionNational Natural Science Foundation of ChinaCenter for Neuromusculoskeletal Restorative Medicine by Innovation and Technology Commission(ITC)of Hong Kong SAR,China(CNRMNational Institutes of HealthNational Institutes of HealthKey Research and Development Program of Hunan ProvinceScience and Technology Innovation Program of Hunan ProvinceScience and Technology Innovation Program of Hunan ProvinceScience and Technology Innovation Program of Hunan ProvinceHunan Provincial Science and Technology Department

2019YFA01119002022YFC36019002022YFC25055008226116039782272560819220179214930682120108009N_CUHK483/22R61-AR073518R01-AR0719302022SK20232023RC10272022RC10092022RC30752023JJ30896

2024

10.1016/j.scib.2024.04.044

科学通报(英文版)
中国科学院

科学通报(英文版)

CSTPCD
ISSN：1001-6538
年,卷(期)：2024.69(12)