| Objective To explore the effect of Tenghuang Jiangu Capsule (TJC) on activation of Wnt5a/β-catenin signaling axis on bone metabolism in ovariectomized (OVX) rats. Methods Fifty rats were randomly chosen from sixty SPF-grade rats for the modeling of ovariectomy. The sixty SPF-grade rats were randomly divided into six groups: sham operation group (SO), ovariectomized model group (OVX), positive control group (ESV), TJC high-dose group (h-TJC), TJC middle- dose group (m-TJC), and TJC low-dose group (l-TJC). Body weight was checked on weekends 2, 4, 6, and 8 after drug intervention. The bone quality changes of the distal femoral metaphysis was evaluated using micro CT on weekend 8 after drug intervention. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) were used to analyze the expression changes of bone metabolism markers. The expression levels of key molecules in the Wnt5a/β-catenin signaling axis were measured using qPCR and Western blotting. Results Compared to the SO group, the OVX group and all TJC dose groups elevated the body weight on weekend 2 after drug intervention. The body weight was also elevated in the OVX group, m-TJC group, and l-TJC group on weekends 4, 6, and 8 after drug intervention, especially in OVX group. The body weight was reduced in h-TJC group on weekend 8 after drug intervention. Compared to those in the SO group, the number of bone trabeculae at the distal femoral metaphysis showed a decreasing trend, the gap between bone trabeculae showed an increasing trend and a phenomenon of cavities, BMD and Tb.N showed a decreasing trend, and Tb.Sp showed an increasing trend. Compared to those in the OVX group, the number of trabeculae at the distal femoral metaphysis in the h-TJC group was similart in the SO group, Tb.N increased, Tb.Sp decreased. BMD showed an upward trend in all doses of TJC groups. Compared to those in the SO group, the levels of BGP showed an downward trend in the OVX group and increased in m-TJC and h-TJC groups. The levels of TRACP showed an upward trend and reduced by all doses of TJC. Compared to those in the SO group, the key molecule expressions of Wnt5a, β-catenin, Col2α, and Runx2 in the Wnt5a/β-catenin signaling axis showed an down-regulation trend. The expression of TRACP showed a up-regulation trend in the OVX group. Compared to those in the OVX group, the mRNA and protein expressions of key molecule Wnt5a, β-catenin, Col2α, and Runx2 were up-regulated in the m-TJC group and h-TJC group. The mRNA expression of TRACP was down-regulated in the m-TJC group and h-TJC group. The protein expression of TRACP was also down-regulated in all dose of TJC groups. Conclusion TJC may inhibit the expression of osteoclast marker molecule TRACP, up-regulate the expressions of osteoblast marker molecules BGP and Col2α by activation of the Wnt5a/β-catenin signaling axis, thus regulate bone metabolism and delay bone loss, producing therapeutic effect on ovariectomized rats. |