Osthole Inhibits Osteoclast Formation and Enhances Bone Mass of Bone Marrow Mesenchymal Stem cells by Activating β-catenin-OPG Signaling Pathway

Summary Osthole has potential therapeutic applications due to its antiosteoporotic. Our study suggested that osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential agent to inhibit bone resorption. Introduction Osthole has potential therapeutic applications due to its antiosteoporotic. we performed study to test if OPG is the target gene of osthole-attenuated osteoclastogenesis. Methods In vivo, using 12-month-old male mice to evaluate the effect of osthole on bone mass. In vitro, Bone marrow stem cells (BMSCs) were isolated, extracted from 3-month-old C57BL/6J mice, 3-month-old β-cateninfx/fx mice, or 3-month-old OPG−/− mice and its littermates of OPG+/+ mice. Results we found that osthole significantly increased the gene and protein levels of OPG expression in primary BMSCs dose-dependently. The deletion of the OPG gene did not affect β-catenin expression and the deletion of the β-catenin gene inhibited OPG expression in BMSCs, which indicated that osthole stimulated the expression of OPG through activation of β-catenin signaling. Conclusion Osthole attenuates osteoclast formation by stimulating the activation of β-catenin-OPG signaling and could be a potential agent to inhibit bone resorption.

Ekspresi IL – 1β pada Proses Kesembuhan Fraktur Os Femur Tikus Putih (Rattus norvegicus) Ovariektomi yang Diterapi dengan Ekstrak Cikal Tulang (Cissus quadrangularis)

This study aims to determine the potential of the Cissus quadrangularis extract to decreased the expression of IL-1 β so that it can to inhibit bone resorption and osteoporosis fracture healing is not delayed union. Forty rats adapted for 1 week, and then divided into four groups with 10 replications. P0 (sham-operated + Osteotomy + CMC Na); P1 (ovariectomy + Osteotomy + CMC Na); P2 (ovariectomy + Osteotomy + Raloxifene 5.4 mg /kg); P3 (ovariectomy + Osteotomy + CQ 750 mg / kg). Osteoporosis induced is made by bilateral ovariectomy in rats, then to make sure that osteoporosis is already happened, 8 weeks post-ovariectomy performed radiology examinations on the femur, then the osteotomy action. IL1-β expression observations performed in at the 2nd week and 6th week after osteotomy through the immunohistochemistry examination. The results of immunohistochemistry examination in the 2nd week showed an increased expression of IL1-β in all groups of rat that did ovariectomy (P1, P2 and P3) were significantly different (p <0.05) with a rat group that didn’t ovariectomy, as well P2 dan P3 were significantly different with P1. The Results of immunohistochemistry examination in the 6th week showed the samepattern with the 2nd week and there is increased IL1-β expression in all groups of rat compared with the results of the examination in the 2nd week. Based on these results it can be concluded that Cissus quadrangularis extract andRaloxifen can decreased the expression of IL-1 β, and the results that don’t significantly different, so that these both materials can to inhibit bone resorption and osteoporosis fracture healing don’t get delayed union.