The effects of cGAS-Sting pathway on bone mineral density

Abstract The cGAS-Sting pathway plays an essential role in a variety of pathological processes, such as inflammation, infection and cancer. It has recently been found to affect bone metabolism, but the exact role is not well understood. We studied the effect of both cGAS gene KO and Sting gene KO mice on bones, and assessed the effects of Sting gene in osteoclast differentiation and osteoblast and formation in vivo. This study found that Sting KO mice but not in cGAS KO mice exhibited a decreased BV/TV and Tb.N, as evident by the micro CT analyses. At the cellular level, Sting deficiency was revealed to promote osteoclastogenesis and inhibit osteoblastogenesis, accompanied with increased phosphorylation of p-38 in osteoclasts and decreased phosphorylation of β-Catenin in bone marrow stromal cells (BMSCs). Our study showed that the absence of cGAS gene had no significant effect on bone density, whereas Sting gene deficiency reduced bone formation in mice, which provides a possible new target for the treatment of osteoporosis.