Tanshinone IIA exerts beneficial effects on fracture healing in vitro and in vivo. - GreenMedInfo Summary
Tanshinone IIA exerts beneficial effects on fracture healing in vitro and in vivo.
Chem Biol Interact. 2019 Sep 1 ;310:108748. Epub 2019 Jul 12. PMID: 31306638
BACKGROUND: Fracture healing is a very important process after fracture. Tanshinone IIA (Tan IIA) has been reported to possess beneficial impact on osteoblasts growth. Our study investigated the effects of Tan IIA on fracture healing.
METHODS: In vitro, mouse pre-osteoblast MC3T3-E1 cells were treated with Tan IIA. Then, the protein levels of Runx2, Osx, Collagen I, JNK and c-Jun, alkaline phosphatase (ALP) activity and calcium deposition were detected, respectively. Furthermore, the roles of microRNA-424 (miR-424) and Bone morphogenetic protein 2 (BMP-2) in Tan IIA-caused MC3T3-E1 cell differentiation were probed. In vivo, mice open osteotomy at femur diaphysis model was established. The callus area, callus intensity, low-density bone volume/callus total volume (BV1/TV), tissue mineral density (TMD) and bone mineral density (BMD) were tested.
RESULTS: In vitro, Tan IIA promoted MC3T3-E1 cell differentiation via increasing the Runx2, Osx and collagen I expression, along with enhancing ALP activity and calcium deposition. In addition, Tan IIA activated JNK pathway in MC3T3-E1 cells, while inhibition of JNK pathway mitigated the Tan IIA-caused MC3T3-E1 cell differentiation. Moreover, Tan IIA declined the miR-424 expression in MC3T3-E1 cells. Overexpression of miR-424 also weakened the Tan IIA-caused MC3T3-E1 cell differentiation. BMP-2 was a target gene of miR-424. BMP-2 silence reversed the Tan IIA-caused activation of JNK pathway. In vivo, Tan IIA increased the callus area, callus intensity, BV1/TV, TMD and BMD.
CONCLUSION: Tan IIA could promote fracture healing. In vitro, Tan IIA promoted MC3T3-E1 cell differentiation might be via down-regulating miR-424, up-regulating BMP-2 and then activating JNK pathway.