Tectoridin inhibits osteoclastogenesis and bone loss in a murine model of ovariectomy-induced osteoporosis.

Abstract

Osteoporosis is a systemic disease that typically affects older adults and that remains a major threat to global public health owing to its high morbidity and mortality rates. In those with osteoporosis, excess osteoclast (OC)-mediated resorption of bone tissue can lead to an imbalance in normal bone metabolism resulting in the onset of diseases including postmenopausal osteoporosis (PMOP). In the present study, we found that the natural Belamcanda chinensis (L.) DC derivative tectoridin can reduce bone loss in ovariectomized mice. TRAP staining further revealed that tectoridin suppresses OC differentiation in a dose-dependent fashion, and qPCR analyses indicated that this compound also dose-dependently inhibits the RANKL-induced upregulation of OC marker genes including Trap, Ctsk, ATP60, DC-Stamp, c-Fos, and NFATc1 in bone marrow macrophages (BMMs). Tectoridin treatment further suppressed actin ring formation and in vitro bone resorption as determined via F-actin staining and scanning electron microscopy. At the mechanistic level, we found that tectoridin was capable of inhibiting osteoclastogenesis at least in part owing to its ability to interfere with NF-κB pathway activation. In addition, we confirmed that tectoridin was able to protect against in vivo estrogen-deficiency-associated bone loss. Together, these results suggest that tectoridin can inhibit osteoclastogenesis and OC functionality in the context of PMOP at least in part via modulating RANKL-induced NF-κB signaling.