New Qiangguyin activates Wnt/β-catenin pathway by down-regulating Notum to improve osteoporosis in rats

Background: Qiangguyin (QGY) is a traditional Chinese medicine prescription for postmenopausal osteoporosis. We modified the formula based on QGY and named it new QGY (N-QGY), and studied the therapeutic mechanism of N-QGY on osteoporosis.

Method: Osteoporosis rat model was established by bilateral ovariectomy, and the rats were treated with exosomes from osteoclasts treated with N-QGY. Then the bone morphological parameters were detected by micro-computed tomography, the levels of Procollagen I N-terminal Propeptide (PINP), β-crosslaps (β-CTX), Estrogen and osteocalcin (OCN) were detected by ELISA, and the expressions of Alkaline Phosphatase (ALP), Runt-related transcription factor 2 (RUNX2), Osteopontin (OPN), Notum and β-catenin were detected by Western blot. Subsequently, the primary cultured bone marrow mesenchymal stem cells (BMSCs) were transfected with Notum overexpression plasmid and co-cultured with exosomes from osteoclasts treated with N-QGY or interleukin (IL)-1β. Subsequently, the cell viability and the expression of bone formation-related genes or proteins were detected. ALP staining and alizarin red staining were performed.

Result: In vivo, N-QGY improved the bone morphological indexes and serum levels of PINP, β-CTX, estrogen, ALP, RUNX2 and OPN in bone tissues or serum, down-regulated Notum expressions and activated β-catenin pathway in bone tissues. The exosomes derived from N-QGY-treated osteoclast alleviated the destructive effect of exosomes derived from osteoclast on osteogenic differentiation of BMSCs, which was embodied in promoting the activity of BMSCs, up-regulating the levels of ALP, RUNX2, OPN and OCN, promoting bone mineralization and activating β-catenin pathway.

Conclusion: N-QGY activates Wnt/β-catenin pathway by down-regulating Notum to improve osteoporosis in rats.

Exosomes derived from osteoclast; New qiangguyin; Notum; Osteoporosis; β-catenin.