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

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

Cell death and differentiation (2017-09-25)
Seung-Ki Min, Hyun Ki Kang, Sung Youn Jung, Da Hyun Jang, Byung-Moo Min
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Integrin β3 Antibody, clone B3A, azide free, clone B3A, Chemicon®, from mouse
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Anti-Integrin α6 Antibody, clone NKI-GoH3, clone NKI-GoH3, Chemicon®, from rat
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Anti-Integrin β1 Antibody, clone 6S6, clone 6S6, Chemicon®, from mouse
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Anti-Integrin α4 Antibody, clone P4C2, ascites fluid, clone P4C2, Chemicon®