Abstract
With rapid economic growth and further developments in medical science, the entry into the aging population is currently increasing, as is the number of patients with metabolic diseases, such as hypertension, hyperlipidemia, heart disease, and diabetes. The current treatments for metabolic bone diseases, which are also on the rise, cause negative side effects. Bisphosphonates, which are used to treat osteoporosis, inhibit the bone resorption ability of osteoclasts and during prolonged administration, cause bisphosphonate‐related osteonecrosis of the jaw (BRONJ). Numerous studies have shown the potential role of natural plant products as flavonoids in the protection against osteoporosis and in the influence of bone remodeling. Autophagy occurs after the degradation of cytoplasmic components within the lysosome and serves as an essential cytoprotective response to pathologic stress caused by certain diseases. In the present study, we hypothesized that the cytoprotective effects of flavonoids might be related to those associated with autophagy, an essential cytoprotective response to the pathologic stress caused by certain diseases, in osteoblasts. We demonstrated the cytoprotective effect of flavonoid‐induced autophagy against the toxicity of zoledronate and the induction of autophagy by flavonoids to support osteogenic transcription factors, leading to osteoblast differentiation and bone formation. Further studies are necessary to clarify the connections between autophagy and osteogenesis. It would be helpful to shed light on methodological challenges through molecular biological studies and new animal models. The findings of the current study may help to delineate the potential role of flavonoids in the treatment of metabolic bone disease.
Highlights
Osteoporosis, a well-known metabolic bone disease, is characterized by a low bone mass and the micro-architectural degeneration of bone tissue.[1,2] The development of metabolic bone disease occurs through imbalances between the formation and resorption of bone by interactions between osteoblasts and osteoclasts.[3]
We investigated the effects of zoledronate on the viability, functions, and osteogenetic and cytoprotective effects of flavonoids, including galangin, icariside II, kaempferol, and quercetin, in human fetal osteoblastic 1.19 cells
The protein levels of collagen I, osteocalcin, bone morphogenetic protein 2 (BMP-2), Alkaline phosphatase (ALP), Osterix, and RUNX2 increased with the combined treatment more than in the group that was just treated with zoledronate (Figure 3C)
Summary
Osteoporosis, a well-known metabolic bone disease, is characterized by a low bone mass and the micro-architectural degeneration of bone tissue.[1,2] The development of metabolic bone disease occurs through imbalances between the formation and resorption of bone by interactions between osteoblasts and osteoclasts.[3]. We investigated the effects of zoledronate on the viability, functions, and osteogenetic and cytoprotective effects of flavonoids, including galangin, icariside II, kaempferol, and quercetin, in human fetal osteoblastic (hFOB) 1.19 cells. The cytotoxicity of zoledronate and the flavonoids (ie, galangin, icariside II, kaempferol, and quercetin) was tested using a tetrazolium dye (MTT) assay, as described in.[25] The hFOB 1.19 cells were treated with zoledronate, galangin, icariside II, kaempferol, and quercetin at various concentrations (0-100 μM) for 24-72 h. The quantification of Alizarin Red S was conducted as described in a previous study.[27] The absorbance of the cells was measured at 550 nm using an ELISA reader (Sunrise Remote Control, Tecan, Austria). Protein lysis and immunoblotting were conducted using previously described methods.[28] Immunostaining with antibodies was performed using a SuperSignal West femtoenhanced chemiluminescence substrate and detected using an TABLE 1 Primers used in this study. A one-way ANOVA was used for Dunnett's multiple-comparison test
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