Osteoporosis is a
bone disease characterized by
low bone mineral density (BMD) and impaired bone microarchitecture due to the abnormal activity of osteoclasts.
Cathelicidins are
antimicrobial peptides present in the lysosomes of macrophages and polymorphonuclear leukocytes. LL-37, a
cathelicidin, induces various biological effects, including modulation of the immune system, angiogenesis, wound healing,
cancer growth, as well as
inflammation, and bone loss. A previous study reported direct involvement of LL-37 suppressing osteoclastogenesis in humans. Here, we examined the role of LL-37 in the treatment of
osteoporosis using an
ovariectomy (OVX) rat model. Our results showed that LL-37 significantly reduced bone loss and pathological injury in OVX rats with
osteoporosis. Furthermore, we found that LL-37 significantly increased the activity of the Wnt/
beta-catenin pathway in OVX rats with
osteoporosis, including the increased expression of
beta-catenin, Osterix (Osx), and Runt-related
transcription factor 2 (Runx2), whereas
XAV-939, an inhibitor of the Wnt/
beta-catenin pathway, significantly blocked the effects of LL-37 on bone loss and abnormal bone metabolism. Altogether, our findings suggested that LL-37 exerted a protective role in regulating bone loss and abnormal bone metabolism in rats with
osteoporosis by activating the Wnt/
beta-catenin pathway.