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AHNAK inhibits osteoporosis progression by stabilizing Smad1 protein
Weifei Zhang1, Hua Chen2, Tiantian Qi3
1Department of Spine Surgery, Shenzhen Second People's Hospital, Affiliated with the First Hospital of Shenzhen University, Shenzhen, 518035, China; Department of Orthopedic Surgery and Orthopedic Research Institute, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, China.
None:
AHNAK is a structural scaffold protein implicated in a wide array of physiological functions. AHNAK mutations are highly prevalent in patients with osteoporosis, However, it is currently unknown whether AHNAK affects the progression of osteoporosis and the specific mechanism behind this effect. This study detected decreased AHNAK (AHNAK1) expression in bone tissues and bone marrow mesenchymal stem cells (BMSCs) of osteoporotic mice. Genetic knockdown of AHNAK inhibited osteogenic differentiation of BMSCs. Mechanistic investigations indicated that AHNAK functions through stabilizing Smad1 protein levels. Overexpression of Smad1 in AHNAK-knockdown BMSCs restored their osteogenic differentiation capacity. Furthermore, in vivo mouse experiments further confirmed these findings. Collectively, these findings indicate that AHNAK inhibits the progression of osteoporosis by stabilizing Smad1 protein.
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