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Cyanidin-3-glucoside Regulates Osteoblast Differentiation via the ERK1/2 Signaling Pathway.

ABSTRACT: Osteoporosis, characterized by a gradual decrease in the number of osteoblasts and a gradual increase in bone resorption of osteoclasts in bone tissue, is a global chronic disease, which severely impairs the quality of life of the elderly. Therefore, it is extremely urgent to study the prevention and treatment of osteoporosis. It has been reported that anthocyanins can regulate bone metabolism and prevent osteoporosis. Cyanidin-3-O-glucoside (C3G), the most common type of anthocyanin in nature, widely exists in a variety of vegetables and fruits. Although it has been shown that C3G has multiple effects on osteoclasts, its impact(s) and underlying mechanism(s) on osteoblasts are still not clear. Here, we evaluated the effect of C3G on cell proliferation and differentiation of osteoblasts (extracted from the hip joint of patients with osteoporosis) and MC3T3-E1 (a kind of osteoblast cell line from mice). We also test the ability of osteoblasts to mineralize after C3G treatment. To find the underlying mechanism of the above effects, we further evaluated the role of the ERK signaling pathway in C3G regulation of osteoblasts. The results showed that C3G treatment enhanced osteoblast proliferation rate, osteoblast mineralization points, the mRNA levels and protein expression levels of OC (osteocalcin), and the level of ERK phosphorylation, which could be blocked by pretreatment with ERK signaling pathway inhibitor. The above results not only indicate that the ERK pathway was involved in C3G regulation of osteoblast differentiation but also provide strong suggestive evidence that osteoblasts may be promising targets in preventive and therapeutic strategies for osteoporosis.

SUBMITTER: Hu B

PROVIDER: S-EPMC7905819 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Cyanidin-3-glucoside Regulates Osteoblast Differentiation via the ERK1/2 Signaling Pathway.

Hu Bosen B Chen Lin L Chen Yong Y Zhang Zhuo Z Wang Xiaohong X Zhou Bo B

ACS omega 20210211 7

Osteoporosis, characterized by a gradual decrease in the number of osteoblasts and a gradual increase in bone resorption of osteoclasts in bone tissue, is a global chronic disease, which severely impairs the quality of life of the elderly. Therefore, it is extremely urgent to study the prevention and treatment of osteoporosis. It has been reported that anthocyanins can regulate bone metabolism and prevent osteoporosis. Cyanidin-3-<i>O</i>-glucoside (C3G), the most common type of anthocyanin in n ...[more]

PMID: 33644583

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Project description:BACKGROUND: Osteoporosis is a worldwide health problem predominantly affecting post-menopausal women. Therapies aimed at increasing bone mass in osteoporetic patients lag behind comparable investigation of therapeutic strategies focusing on the bone resorption process. Sesamin, a major lignan compound found in Sesamun indicum Linn., has a variety of pharmacological effects, though its activity on bone cell function is unclear. Herein we examine the effect of this lignan on osteoblast differentiation and function. METHOD: Cell cytotoxicity and proliferative in hFOB1.19 were examined by MTT and alamar blue assay up to 96 h of treatment. Gene expression of COL1, ALP, BMP-2, Runx2, OC, RANKL and OPG were detected after 24 h of sesamin treatment. ALP activity was measured at day 7, 14 and 21 of cultured. For mineralized assay, ADSCs were cultured in the presence of osteogenic media supplement with or without sesamin for 21 days and then stained with Alizarin Red S. MAPK signaling pathway activation was observed by using western blotting. RESULTS: Sesamin promoted the gene expression of COL1, ALP, OCN, BMP-2 and Runx2 in hFOB1.19. On the other hand, sesamin was able to up-regulate OPG and down-regulate RANKL gene expression. ALP activity also significantly increased after sesamin treatment. Interestingly, sesamin induced formation of mineralized nodules in adipose derived stem cells (ADSCs) as observed by Alizarin Red S staining; this implies that sesamin has anabolic effects both on progenitor and committed cell stages of osteoblasts. Western blotting data showed that sesamin activated phosphorylation of p38 and ERK1/2 in hFOB1.19. CONCLUSIONS: The data suggest that sesamin has the ability to trigger osteoblast differentiation by activation of the p38 and ERK MAPK signaling pathway and possibly indirectly regulate osteoclast development via the expression of OPG and RANKL in osteoblasts. Therefore, sesamin may be a promising phytochemical that could be developed for supplementation of osteoporotic therapy.

Project description:BackgroundOncostatin M receptor (OSMR), as one of the receptors for oncostatin M (OSM), has previously been shown to mediate the stimulatory role of OSM in osteoclastogenesis and bone resorption. However, it remains to be clarified whether and how OSMR affects the differentiation of osteoblasts.MethodsThe expression level of OSMR during osteoblast and adipocyte differentiation was examined. The role of OSMR in the differentiation was investigated using in vitro gain-of-function and loss-of-function experiments. The mechanisms by which OSMR regulates bone cell differentiation were explored. Finally, in vivo function of OSMR in cell fate determination and bone homeostasis was studied after transplantation of OSMR-silenced bone marrow stromal cells (BMSCs) to the marrow of ovariectomized mice.ResultsOSMR was regulated during osteogenic and adipogenic differentiation of marrow stromal progenitor cells and increased in the metaphysis of ovariectomized mice. OSMR suppressed osteogenic differentiation and stimulated adipogenic differentiation of progenitor cells. Mechanistic investigations showed that OSMR inhibited extracellular signal-regulated kinase (ERK) and autophagy signaling. The downregulation of autophagy, which was mediated by ERK inhibition, suppressed osteogenic differentiation of progenitor cells. Additionally, inactivation of ERK/autophagy signaling attenuated the stimulation of osteogenic differentiation induced by Osmr siRNA. Furthermore, transplantation of BMSCs in which OSMR was silenced to the marrow of mice promoted osteoblast differentiation, attenuated fat accumulation and osteoclast differentiation, and thereby relieved the osteopenic phenotype in the ovariectomized mice.ConclusionsOur study has for the first time established the direct role of OSMR in regulating osteogenic differentiation of marrow stromal progenitor cells through ERK-mediated autophagy signaling. OSMR thus contributes to bone homeostasis through dual regulation of osteoblasts and osteoclasts. It also suggests that OSMR may be a potential target for the treatment of metabolic disorders such as osteoporosis.

Project description:Grb2-associated binder 1 (Gab1) coordinates various receptor tyrosine kinase signaling pathways. Although skeletal muscle differentiation is regulated by some growth factors, it remains elusive whether Gab1 coordinates myogenic signals. Here, we examined the molecular mechanism of insulin-like growth factor-I (IGF-I)-mediated myogenic differentiation, focusing on Gab1 and its downstream signaling. Gab1 underwent tyrosine phosphorylation and subsequent complex formation with protein-tyrosine phosphatase SHP2 upon IGF-I stimulation in C2C12 myoblasts. On the other hand, Gab1 constitutively associated with phosphatidylinositol 3-kinase regulatory subunit p85. To delineate the role of Gab1 in IGF-I-dependent signaling, we examined the effect of adenovirus-mediated forced expression of wild-type Gab1 (Gab1(WT)), mutated Gab1 that is unable to bind SHP2 (Gab1(DeltaSHP2)), or mutated Gab1 that is unable to bind p85 (Gab1(Deltap85)), on the differentiation of C2C12 myoblasts. IGF-I-induced myogenic differentiation was enhanced in myoblasts overexpressing Gab1(DeltaSHP2), but inhibited in those overexpressing either Gab1(WT) or Gab1(Deltap85). Conversely, IGF-I-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation was significantly repressed in myoblasts overexpressing Gab1(DeltaSHP2) but enhanced in those overexpressing either Gab1(WT) or Gab1(Deltap85). Furthermore, small interference RNA-mediated Gab1 knockdown enhanced myogenic differentiation. Overexpression of catalytic-inactive SHP2 modulated IGF-I-induced myogenic differentiation and ERK1/2 activation similarly to that of Gab1(DeltaSHP2), suggesting that Gab1-SHP2 complex inhibits IGF-I-dependent myogenesis through ERK1/2. Consistently, the blockade of ERK1/2 pathway reversed the inhibitory effect of Gab1(WT) overexpression on myogenic differentiation, and constitutive activation of the ERK1/2 pathway suppressed the enhanced myogenic differentiation by overexpression of Gab1(DeltaSHP2). Collectively, these data suggest that the Gab1-SHP2-ERK1/2 signaling pathway comprises an inhibitory axis for IGF-I-dependent myogenic differentiation.

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Cyanidin-3-glucoside Regulates Osteoblast Differentiation via the ERK1/2 Signaling Pathway.

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Cyanidin-3-glucoside Regulates Osteoblast Differentiation via the ERK1/2 Signaling Pathway.

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