A vitronectin-derived peptide reverses ovariectomy-induced bone loss via regulation of osteoblast and osteoclast differentiation

Abstract

Osteoporosis affects millions of people worldwide by promoting bone resorption and impairing bone formation. Bisphosphonates, commonly used agents to treat osteoporosis, cannot reverse the substantial bone loss that has already occurred by the time of diagnosis. Moreover, their undesirable side-effects, including osteonecrosis of the jaw, have been reported. Here, we demonstrated that a new bioactive core vitronectin-derived peptide (VnP-16) promoted bone formation by accelerating osteoblast differentiation and activity through direct interaction with β1 integrin followed by FAK activation. Concomitantly, VnP-16 inhibited bone resorption by restraining JNK-c-Fos-NFATc1-induced osteoclast differentiation and αvβ3 integrin-c-Src-PYK2-mediated resorptive function. Moreover, VnP-16 decreased the bone resorbing activity of pre-existing mature osteoclasts without changing their survival rate. Furthermore, VnP-16 had a strong anabolic effect on bone regeneration by stimulating osteoblast differentiation and increasing osteoblast number, and significantly alleviated proinflammatory cytokine-induced bone resorption by restraining osteoclast differentiation and function in murine models. Moreover, VnP-16 could reverse ovariectomy-induced bone loss by both inhibiting bone resorption and promoting bone formation. Given its dual role in promoting bone formation and inhibiting bone resorption, our results suggest that VnP-16 could be an attractive therapeutic agent for treating osteoporosis.

Regulation of osteogenesis and osteoclastogenesis by zoledronic acid loaded on biodegradable magnesium-strontium alloy

“…NFATC1 regulates the expression of numerous osteoclasogenic genes, and it has been reported that embryonic stem cells with NFATC1-genetic deficiency cannot differentiate into mature osteoclasts 41 . c-Src influences bone absorption through mediating the adhesion and migration of osteoclasts 42 . CTSK and MMP-9 involve in the degradation of bone matrix and then induce the activation of bone-resorptive 43 .…”

Anti-Osteoporotic Effects of Antioxidant Peptides PIISVYWK and FSVVPSPK from Mytilus edulis on Ovariectomized Mice

“…There have been attempts to develop anti-osteoporosis agents without side-effects. In recent years, several BAPs with a potential anti-osteoporotic effect have been developed from various endogenous proteins [ 12 , 17 , 18 ]. In addition, BAPs that could stimulate osteoblast differentiation and showed an anti-osteoporotic effect have also been developed from food proteins by enzymatic hydrolysis [ 10 , 11 , 19 , 20 ].…”

Modifications of Dental Implant Surfaces at the Micro- and Nano-Level for Enhanced Osseointegration

“…The mechanism behind the superior bone cell responses has been tried to be explained, based on the hypothesized tunable allosteric control of the receptor proteins [67,70]. A recent investigation evaluating a functional peptide from vitronectin found a Janus effect of this peptide for bone formation, activating osteoblasts and inhibiting osteoclasts, that is, controlling the osteoporotic environment locally to be favorable for osseointegration [71].…”