Abstract
Corylin, a flavonoid isolated from the fruit of Psoralea corylifolia, has an osteogenic effect on osteoblasts in vitro and bone micromass ex vivo. However, the effect and mechanism of corylin in regulating osteoclastogenesis remain unknown. By using murine bone marrow macrophages as the osteoclast precursor, corylin was found to inhibit the receptor activator of nuclear factor (NF) κB ligand (RANKL)-induced osteoclast differentiation via down-regulating osteoclastic marker genes. In parallel, F-actin formation and osteoclast migration were diminished in corylin-treated cultured osteoclasts, and subsequently the expressions of osteoclastic proteins were suppressed: the suppression of protein expression was further illustrated by transcriptomic analysis. Furthermore, corylin inhibited the nuclear translocation of p65, giving rise to a restraint in osteoclastic differentiation through the attenuation of transcription factors nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and nuclear factor of activated T cells c1 (NFATc1). There was no obvious change in apoptosis when the RANKL-induce osteoclasts were cultured in the presence of corylin. The finding supports the potential development of corylin as an osteoclast inhibitor against osteoporosis.
Highlights
The activity of tartrate-resistant acid phosphatase (TRAP), an enzyme actively expressed by osteoclasts, was increased in a time-dependent manner after the stimulation of RANKL in cultures (Figure 2b)
This activity was significantly inhibited by corylin in a concentrationdependent manner after 4 days of treatment; TRAP activity was not affected by corylin during the early stages of osteoclastogenesis, i.e., from 1–3 days of treatment (Figure 2b)
In the treatment of the RANKL control (MCSF + RANKL), cultured bone marrow macrophages obviously differentiated into multi-nucleated TRAPpositive cells, an indicative marker of osteoclasts (Figure 2c)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Characterized by low bone mass density and degradative microarchitecture, osteoporosis is a systemic skeletal disease and age-related metabolic disorder. This medical problem is commonly occurring today, in post-menopausal women and the aged population [1]. Considered as a “silent killer” disease, osteoporosis has been widely regarded as a major public health problem [2]. The so called “brittle bone” or “porous bone” increases the susceptibility to bone fracture that causes disability and chronic pain
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