Abstract

Vitis thunbergii is used in Taiwan as a botanical supplement for inflammatory bone diseases. This study aims to examine its direct effect on bone metabolism. Three-month-old female mice were randomly divided into ovariectomized control (OVX), sham operated (SHAM), and ovariectomy treated with either 17β-estradiol or a special ingredient (VtR) fractionated from an ethanol extract of V. thunbergii started two weeks after ovariectomy. VtR treatment for 8 weeks significantly ameliorated the deterioration of bone mineral density and reversed all the ovariectomy-induced changes in μ-CT parameters. The antiosteoporotic effect of VtR accompanied decrease in serum levels of C-terminal telopeptides of type I collagen (CTx), interleukin-7, and ration of RANKL/osteoprotegerin (OPG) but rise in osteocalcin concentration. Sparse calcified microarchitecture and less alkaline-phosphatase- (ALP-) positive cells were observed at the femur and vertebral sites in OVX mice while VtR remarkably restored such variation. HPLC analysis showed (+)-vitisin-A, (−)-vitisin-B, and ampelopsin C predominated in VtR. Both (−)-vitisin B and ampelopsin C increased ALP activity and bone nodule formation in cultured osteoblasts. Instead of stimulating osteoblastogenesis, (+)-vitisin A dramatically repressed osteoclasts differentiation and bone resorption. The results suggested VtR composed of diverse components to reciprocally drive osteoblastogenesis and interdict osteoclastogenesis may serve as a potential botanic drug for osteoporosis therapy.

Highlights

  • Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of the microarchitecture of bone tissue which is attributed to various factors including inflammation and aging [1]

  • The body weight of the OVX group continued to be significantly higher than the sham operated (SHAM) group throughout the study. 17β-Estradiol (E) completely prevented the increase in body weight associated with estrogen deficiency and returned the body

  • None of the tested compounds significantly affected osteoclast growth at a concentration of 20 μM over a 4-day culture period. We further studied their effects on osteoclastogenesis by determining the osteoclast differentiation marker tartrate-resistant acid phosphatase (TRAP) after the stimulation of bone marrow macrophages (BMMs) with recombinant RANKL in the presence of macrophagecolony stimulating factor (M-CSF)

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Summary

Introduction

Osteoporosis is characterized by skeletal degeneration with low bone mass and destruction of the microarchitecture of bone tissue which is attributed to various factors including inflammation and aging [1]. Women are more likely to develop osteoporosis than men due to the reduction in estrogen during menopause, leading to decreased bone-formation (mediated by osteoblasts) and increased bone-resorption (mediated by osteoclasts) activity. Available agents used to treat osteoporosis are major based on the inhibition of osteoclastic bone resorption to prevent further bone loss [2]. Drugs with anabolic effects have recently received much attention for osteoporosis therapy. These pharmacologic agents can stimulate new bone formation, enhance bone density, reduce bone fracture, and promote bone health. Accumulating use experience in Taiwan revealed an alcoholic drench of the roots of V. thunbergii cures bone fractures and contusions and prevents bone loss, suggesting that this herb might stimulate new bone formation and accelerate fracture healing.

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