Scutellarin enhances osteoblast proliferation and function via NF-κB-mediated CXCR4 induction

In the current study, we aimed to examine the function of scutellarin on human osteoblast proliferation and osteogenic function. The results indicated that scutellarin enhanced osteoblast proliferation over a seven day period. This increase in cell proliferation was associated with corresponding increases in osteoblast activity, as measured by alkaline phosphatase (ALP) secretion, intracellular calcium ion influx, and calcium deposition. These anabolic effects were associated with C-X-C chemokine receptor type 4 (CXCR4) mRNA levels and protein induction. Knockdown of CXCR4 reversed the scutellarin-induced increases in cell proliferation, ALP activity, and calcium deposition. Furthermore, scutellarin increased p65 phosphorylation in a dose-dependent manner, which resulted in the increased binding of phosphorylated p65 to the CXCR4 gene promoter region, to increase CXCR4 protein expression. p65 phosphorylation inhibition resulted in a decrease in CXCR4 protein expression. A p65 inhibitor blocked scutellarin-induced increases in osteoblast proliferation and function. Moreover, in a rat model of estrogen-deficient osteoporosis, scutellarin restored ovariectomy-induced bone loss in mice. Taken together, both cellular and animal models support the novel findings that scutellarin increased osteoblast proliferation and function through NF-κB/p65-mediated CXCR4 induction.