Tanshinone IIA exerts beneficial effects on fracture healing in vitro and in vivo.

PMID: 

Chem Biol Interact. 2019 Sep 1 ;310:108748. Epub 2019 Jul 12. PMID: 31306638

Abstract Title: 

Tanshinone IIA exerts beneficial effects on fracture healing in vitro and in vivo.

Abstract: 

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.

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