Abstract
Osteoporosis is the most common aging-associated bone disease and is caused by hyperactivation of osteoclastic activity. We previously reported that the hexane extract of ginger rhizome [ginger hexane extract (GHE)] could suppress receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in RAW264.7 cells. However, the anti-osteoclastic components in GHE have not yet been identified. In this study, we separated GHE into several fractions using silica gel column chromatography and evaluated their effects on osteoclastogenesis using a RAW264.7 cell osteoclast differentiation assay (in vitro) and the zebrafish scale model of osteoporosis (in vivo). We identified that the fractions containing 10-gingerol suppressed osteoclastogenesis in RAW264.7 cells detected by tartrate-resistant acid phosphatase (TRAP) staining. In zebrafish, GHE and 10-gingerol suppressed osteoclastogenesis in prednisolone-induced osteoporosis regenerated scales to promote normal regeneration. Gene expression analysis revealed that 10-gingerol suppressed osteoclast markers in RAW264.7 cells [osteoclast-associated immunoglobulin-like receptor, dendrocyte-expressed seven transmembrane protein, and matrix metallopeptidase-9 (Mmp9)] and zebrafish scales [osteoclast-specific cathepsin K (CTSK), mmp2, and mmp9]. Interestingly, nuclear factor of activated T-cells cytoplasmic 1, a master transcription regulator of osteoclast differentiation upstream of the osteoclastic activators, was downregulated in zebrafish scales but showed no alteration in RAW264.7 cells. In addition, 10-gingerol inhibited CTSK activity under cell-free conditions. This is the first study, to our knowledge, that has found that 10-gingerol in GHE could suppress osteoclastic activity in both in vitro and in vivo conditions.
Highlights
Osteoporosis is a progressive metabolic disease in which the bone structure deteriorates due to a decrease in bone density associated with aging and lifestyle factors
tartrate-resistant acid phosphatase (TRAP) staining can be used to detect osteoclasts as TRAP is a well-known marker of osteoclast resorption in bone metabolism
Representative images of TRAPstained RAW264.7 cells with ginger hexane extract (GHE) or each fraction are depicted in Supplementary Figure 1
Summary
Osteoporosis is a progressive metabolic disease in which the bone structure deteriorates due to a decrease in bone density associated with aging and lifestyle factors. The pharmacological treatment of osteoporosis is to inhibit osteoclast activities or decrease the number of osteoclasts present to promote bone formation. Bisphosphonates, a class of chemicals that are most commonly used to treat osteoporosis, are adsorbed onto bone surfaces and taken up by osteoclasts to induce apoptosis and promote bone formation (Drake et al, 2008; Rogers et al, 2011). Bisphosphonates directly inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated osteoclast differentiation and fusion in RAW264.7 cells (Abe et al, 2012). Soybean isoflavone acts as a female hormone analog in maintaining bone metabolism in postmenopausal women (Wei et al, 2012), and citrus β-cryptoxanthin promote bone formation and suppresses osteoclastogenesis in tissue cultures (Yamaguchi and Uchiyama, 2004)
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