Abstract

Gushukang (GSK) is a traditional herbal compound used in Chinese medicine for the treatment of osteoporosis. Numerous studies have been conducted to elucidate the effects of GSK, but the mechanisms underlying these effects remain unclear. In the present study, we cultured osteoblasts and osteoclasts with low and high doses of GSK, and also administered 3-month-old mice with 4 and 8 g/kg/day of GSK solution. Gushukang was found to promote osteoblast differentiation and inhibit osteoclast differentiation in vitro. In vivo, mice in the GSK treatment groups showed an increase in bone mass, as measured by micro-computed tomography (Micro-CT). Tartrate resistant acid phosphatase (TRAP) staining and osteocalcin (OCN) staining experiments revealed decreased bone resorption and increased bone formation in the GSK treatment groups. In addition, we found a novel effect of GSK—it could induce type-H vessel formation in mice. The underlying mechanisms of these actions were further explored at the molecular level to investigate whether these effects were due to an overexpression of the hypoxia inducible factor-1 (HIF-1α). Our findings indicate the utility of GSK as a therapeutic for the prevention of osteoporosis.

Highlights

  • Primary osteoporosis is a bone disease characterized by decreased bone mass and bone density, resulting from estrogen deficiency and aging (Ng et al, 2015; Wang et al, 2015; Su et al, 2019; Rendina-Ruedy and Rosen, 2020)

  • We found that the GSK-treated mice had higher values of bone mineral density (BMD) than the control group mice (Figure 1A)

  • Mice treated with a low dose of GSK had a lower BMD than mice treated with a high dose of GSK

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Summary

Introduction

Primary osteoporosis is a bone disease characterized by decreased bone mass and bone density, resulting from estrogen deficiency and aging (Ng et al, 2015; Wang et al, 2015; Su et al, 2019; Rendina-Ruedy and Rosen, 2020). The current treatment for osteoporosis comprises antiresorptive and bone-forming medicines (Cao et al, 2018), including estrogens (Hayashi et al, 2019), parathyroid hormone (Fan et al, 2017), bisphosphonates (Wei et al, 2016), and drugs, which blockade follicular stimulating hormone (Sponton and Kajimura, 2017). Most of these treatments concentrate on a single aspect of the disease, and thorough assessments of their efficacy and safety is still needed (Rauch et al, 2010). Gushukang has already been approved for listing in the Chinese Pharmacopeia for the prevention and treatment of osteoporosis

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