Beneficial effect of pristimerin against the development of osteoporosis in ovariectomy-induced osteoporosis rats by the RANKL/TRAF6/NF-KB pathway

Introduction: Osteoporosis is a major cause of bone fracture in post -meno-pausal women. We evaluated the effects of pristimerin treatment on ova- riectomy-induced osteoporosis, and its possible molecular mechanism.Material and methods: Rats were ovariectomised and biochemical markers of bone formation were determined from serum samples. The microarchitec-tures of bone tissues were analyzed via micro-CT scans and Western blot-ting assays. The cytotoxic effects of pristimerin, the differentiation of osteo-clasts, and bone reabsorption were evaluated in vitro using RAW 264.7 cells. Results: Treatment with pristimerin attenuated changes in markers of bone formation and reabsorption such as creatine kinase (CK), alkaline phospha-tase (ALP), tartrate-resistant acid phosphatase (TRAP), collagen type I frag-ments (CTX), bone Gla-protein (BGP), and osteocalcin (OC) in the serum of ovariectomised rats. It also appeared to restore the microarchitecture of bone tissue. The expression levels of TNF receptor-associated factor 6 (TRAF-6), nuclear factor K light chain enhancer of activated B cells (NF-KB p65), and receptor activator of nuclear factor-KB ligand (RANKL) protein were significantly lower, while those of Akt and PI3K were significantly high-er, in the bone tissues of the pristimerin-treated group than in negative controls. Pristimerin had no cytotoxic effect on RAW 264.7 cells and reduced the differentiation of osteoclasts, bone reabsorption, and translocation of p65 in RANKL-stimulated RAW 264.7 cells in vitro.Conclusions: Pristimerin reduces the effects of osteoporosis by restoring the altered RANKL/TRAF-6/NF-KB pathway in ovariectomised rats.