Dendrobine promotes bone formation via the canonical Wnt/β-catenin signaling 1 pathway and prevents postmenopausal osteoporosis

Shengfa Li¹Peili Liang²Jian Chen³Youming Zhang⁴Haixiong Miao^5*Ting Wang^1*

• ¹Chengdu Third People's Hospital, Chengdu, China
• ²Key Laboratory for Major Obstetric Diseases of Guangdong Province, Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong Province, China
• ³Chongqing Three Gorges Central Hospital, Chongqing, China
• ⁴Department of Chemical Engineering, School of Materials Science and Engineering, Tsinghua University, Beijing, China
• ⁵Department of Orthopedics, Guangzhou Red Cross Hospital, Guangzhou, Guangdong Province, China

Abstract Background: During early postmenopausal women with sex steroid deficiency, an imbalance between bone resorption and bone formation causes an accelerated decline in bone mineral density due to a longer lifespan of osteoclasts and a shorter lifespan of osteoblasts. Given this context, dendrobine, as a primary bioactive alkaloid isolated from Dendrobium nobile Lindl., had potential efficacy on osteoporosis due to the traditional use of Dendrobium nobile Lindl. in musculoskeletal disease. Objective: To investigate whether dendrobine had antiosteoporotic efficacy in increasing osteoblastogenesis and illustrated the underlying mechanism. Methods: Using C3H/10T1/2 cells and human bone marrow-derived mesenchymal stromal cells, the effects of dendrobine on osteoblastogenesis and underlying mechanism were assayed by western blotting, alkaline phosphatase staining, and quantitative polymerase chain reaction. The effectiveness of dendrobine in preventing postmenopausal osteoporosis was assessed using an ovariectomized mouse model by micro-computed tomography, H&E, alkaline phosphatase, and immunohistochemical staining. Results: Aside from inducing alkaline phosphatase, Runx2, osteocalcin, and osterix expression in C3H/10T1/2 cells, Dendrobine increased Runx2, alkaline phosphatase, and osteocalcin expression in ovariectomy (OVX) mice. Conclusion: In OVX mice, dendrobine attenuated the loss of cancellous bone, as shown in micro-computed tomography analysis. Dendrobine activated the Wnt/β-catenin pathway by suppressing the phosphorylation level of GSK-3β at Tyr216 site while keeping the level of β-catenin sustaining. Dendrobine activated the Wnt/β-catenin pathway by suppressing the phosphorylation of GSK-3β at Tyr216. This study suggests that dendrobine may be an effective treatment for postmenopausal osteoporosis.