2. Academic Validation
  3. Targeting Filamin A alleviates ovariectomy-induced bone loss in mice via the WNT/β-catenin signaling pathway

Targeting Filamin A alleviates ovariectomy-induced bone loss in mice via the WNT/β-catenin signaling pathway

  • Cell Signal. 2022 Feb;90:110191. doi: 10.1016/j.cellsig.2021.110191.
Changsheng Yang 1,  Panpan Yang 2,  Peilin Liu 2,  Hong Wang 2,  Ee Ke 3,  Kai Li 4,  Huibo Yan 5
Affiliations

Affiliations

  • 1 Department of Spine Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, Guangdong Province 510000, China.
  • 2 Academy of Orthopedics Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province 510000, China.
  • 3 Guangdong Provincial People's Hospital, Guangdong, Academy of Medical Sciences, Guangzhou 510080, China. Electronic address: elieen_ke@126.com.
  • 4 Academy of Orthopedics Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province 510000, China. Electronic address: lk516433415@smu.edu.cn.
  • 5 Department of Spine Surgery, The Third Affiliated Hospital of Southern Medical University, Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Guangzhou, Guangdong Province 510000, China. Electronic address: yhb2096@163.com.
PMID: 34774991 DOI: 10.1016/j.cellsig.2021.110191
Abstract

Osteoporosis (OP) is a worldwide prevalent chronic metabolic bone disease, causing by a disruption of the balance between bone resorption and formation. Estrogen deficiency and aging are the main causes for disturbances in bone remodeling activity and bone loss, however, the mechanisms underlying bone remodeling regulation require clarification if novel targets for OP treatment are to be identified. In this investigation, we showed that filamin A (FLNA) accumulated in osteoblasts (OBs) and osteoclasts (OC) in bone from human OP samples, and mice with age-related and postmenopausal OP. FLNA negatively modulated in vitro osteogenic differentiation and positively promoted RANKL-induced osteoclastic differentiation. Mechanistically, FLNA interacted with low-density lipoprotein receptor-related proteins 6 (LRP6) to inhibit β-catenin expression, and enhanced nuclear factor of activated T cell c1 (NFATc1)-dependent osteoclastogenic gene expression to inhibit osteogenesis, and promote osteoclastogenesis. Inhibiting FLNA with calpeptin activated Wnt/β-catenin signaling, resulting in prominent protective effects of bone loss in ovariectomy (OVX)-induced postmenopausal OP mice. Our findings revealed that FLNA not only participated in OP pathogenesis, but could be a new target to stimulate bone formation and inhibit bone resorption. Targeting FLNA with calpeptin may be a promising therapeutic approach for postmenopausal OP in the future.

Keywords

Bone remodeling; Calpeptin; Filamin A; Osteoporosis; WNT/β-catenin signaling.

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