Water extract of Spatholobus suberectus inhibits osteoclast differentiation and bone resorption

Hyunil Ha,Hyosun An,Taesoo Kim,Jin Yeul Ma,Ki-Shuk Shim

doi:10.1186/1472-6882-13-112

Abstract

BackgroundOsteoclasts are primarily responsible for bone resorption. In many pathological bone diseases including osteoporosis and rheumatoid arthritis, osteoclasts are excessively activated. Thus, controlling of osteoclasts would be an effective therapeutic strategy for the treatment of excessive bone loss. The stem of Spatholobus suberectus has been widely used in traditional medicine to treat blood stasis syndrome and arthritis in Asia. In the present study, we investigated the effects and action mechanism of water extract of the stem of Spatholobus suberectus (WESS) on osteoclast differentiation and function.MethodsThe effect of WESS on osteoclast differentiation was evaluated by counting tartrate resistant acid phosphatase-positive multinucleated cells in bone marrow-derived macrophages system and murine bone marrow cell-osteoblast coculture system. Bone resorption activity of mature osteoclast was examined on a calcium phosphate-coated plate. Actin ring structure of osteoclasts was detected fluorescently by staining for F-actin. Activation of signaling pathways and induction of transcription factors required for osteoclastogenesis were investigated by real-time PCR and Western blotting.ResultsWESS effectively inhibited osteoclast differentiation from its precursors. The inhibitory effect of WESS on osteoclast differentiation was due to the suppression of osteoclastogenic transcription factors, c-Fos and nuclear factor of activated T cells cytoplasmic 1 expression, via preventing receptor activator of nuclear factor-κB ligand-induced early signaling pathways and decreasing c-Fos protein level in osteoclast precursors. Furthermore, WESS suppressed bone resorption activity of osteoclasts by disrupting actin ring structure.ConclusionsThis study demonstrated that WESS inhibits osteoclast differentiation and function. These results suggest that WESS has a potential for treating pathological bone diseases caused by excessive bone resorption.

Highlights

Osteoclasts are primarily responsible for bone resorption
To investigate whether WESS affects the ability of osteoblasts to support osteoclast differentiation, we tested in bone marrow cell-osteoblast coculture system
Effect of WESS on RANKL-induced c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) expression To address the inhibitory mechanism of WESS on RANKL-induced osteoclastogenesis, we explored the effect of WESS on the expression of c-Fos and NFATc1, key transcription factors for osteoclast differentiation [8,9]

Summary

Introduction

Osteoclasts are primarily responsible for bone resorption. In many pathological bone diseases including osteoporosis and rheumatoid arthritis, osteoclasts are excessively activated. Progressive and excessive bone resorption by osteoclasts than bone formation causes an imbalance of bone remodeling which is characterized in several pathological bone diseases including osteoporosis, Paget’s disease, and rheumatoid arthritis [1]. Upon binding to its receptor RANK on the cell surface of osteoclast precursors, RANKL induces the recruitment of adaptor molecules such as tumor necrosis factor receptorassociated factor 6, which activates multiple downstream signaling molecules including mitogen-activated protein kinases (MAPKs) and NF-κB. These signaling pathways in turn lead to induction and activation of transcription factors required for osteoclast differentiation and activation [6]. NFATc1 functions as a master transcription factor for osteoclast differentiation, and its induction is dependent on c-Fos [9,10]

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Results

Discussion

Conclusion