Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression

Han, Sang‐Yong; Kim, Yun-Kyung

doi:10.1142/s0192415x19500228

Cited by 37 publications

(25 citation statements)

References 48 publications

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“…OSCAR is specifically expressed in early stage osteoclasts or in mature osteoclasts, and induces calcium activation to assist in the expression of RANKL-mediated NFATc1 (54). Similar to these results, the majority of osteoclast inhibition studies have reported that osteoclast-related genes are decreased by reduction of c-Fos and NFATc1 (55,56). OC-STAMP and ATP6v0d2 are expressed when the osteoclast precursor cells are fused, and when it is deficient, differentiation into osteoclasts is not completed.…”

Section: Discussionsupporting

confidence: 81%

Leonurus�sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation

Kim

Jung

et al. 2019

Int J Mol Med

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Leonurus sibiricus L. (LS) is a medicinal plant used in East Asia, Europe and the USA. LS is primarily used in the treatment of gynecological diseases, and recent studies have demonstrated that it exerts anti-inflammatory and antioxidant effects. To the best of our knowledge, the present study demonstrated for the first time that LS may promote osteoblast differentiation and suppress osteoclast differentiation in vitro , and that it inhibited lipopolysaccharide (LPS)-induced bone loss in a mouse model. LS was observed to promote the osteoblast differentiation of MC3T3-E1 cells and upregulate the expression of runt-related transcription factor 2 (RUNX2), a key gene involved in osteoblast differentiation. This resulted in the induction of the expression of various osteogenic genes, including alkaline phosphatase (ALP), osteonectin (OSN), osteopontin (OPN), type I collagen (COL1) and bone sialoprotein (BSP). LS was also observed to inhibit osteoclast differentiation and bone resorption. The expression levels of nuclear factor of activated T-cells 1 (NFATc1) and c-Fos were inhibited following LS treatment. NFATc1 and c-Fos are key markers of osteoclast differentiation that inhibit receptor activator of nuclear factor-κB ligand (RANKL)-induced mitogen-activated protein kinase (MAPKs) and nuclear factor (NF)-κB. As a result, LS suppressed the expression of osteoclast-associated genes, such as matrix metallopeptidase-9 (MMP-9), cathepsin K (Ctsk), tartrate-resistant acid phosphatase (TRAP), osteoclast-associated immunoglobulin-like receptor (OSCAR), c-src, c-myc, osteoclast stimulatory transmembrane protein (OC-STAMP) and ATPase H+ transporting V0 subunit d2 (ATP6v0d2). Consistent with the in vitro results, LS inhibited the reduction in bone mineral density and the bone volume/total volume ratio in a mouse model of LPS-induced osteoporosis. These results suggest that LS may be a valuable agent for the treatment of osteoporosis and additional bone metabolic diseases.

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Section: Discussionsupporting

confidence: 81%

Leonurus�sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation

Kim

Jung

et al. 2019

Int J Mol Med

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“…There are two pathways for osteoclast proliferation, differentiation, and maturation, 38 and the main pathway is the RANKL/RANK/OPG system, which has been expressed in the early stage of OP. 39 The secondary pathway is the pathway of inflammatory factors. 40 RANKL is the only factor currently found to induce osteoclast differentiation, development, and function.…”

Section: Discussionmentioning

confidence: 99%

“…It’s well known that microRNAs can inhibit the expression of target genes by binding to complementary segments of messenger RNA and interfering with the formation of proteins by translation. 39 Previous studies have found that miR-93-5p and miR-378 were involved in the regulation of OP by binding to BMP-2, a number of active bone morphogenetic proteins. 46 , 47 Therefore, BMP-2 may play a critical role in miRNA-mediated regulation of OP.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-151a-3p Functions in the Regulation of Osteoclast Differentiation: Significance to Postmenopausal Osteoporosis

He¹,

Chen²,

Guo³

et al. 2021

CIA

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Background: Studies have found the pivotal role of miRNAs in the progression of postmenopausal osteoporosis (OP). However, the function of miRNAs in OP is unclear. This study aimed to explore the biological functions of microRNA-151a-3p in OP. Methods: RT-qPCR was employed to assess the expression of microRNA-151a-3p in serum isolated from OP patients and healthy controls. Dual-energy X-ray absorptiometry (DXA) was used to measure the bone mineral density (BMD) of the lumbar spine. The expression levels of c-Fos, NFATc1, and TRAP were tested by Western blot. Ovariectomized (OVX) rats were treated with antago microRNA-151a-3p or antago NC, and then serum and lumbar vertebrae were collected for ELISA and bone histomorphology analysis. Results: The expression of microRNA-151a-3p in postmenopausal women with osteoporosis was significantly up-regulated, and microRNA-151a-3p level was negatively correlated with BMD. During osteoclastogenesis, microRNA-151a-3p level was obviously increased. Overexpression of microRNA-151a-3p promoted the differentiation of RANKL-induced THP-1 and RAW264.7 cells into osteoclasts, whereas silencing of microRNA-151a-3p resulted in the opposite results. Silencing of microRNA-151a-3p in OVX rats altered osteoclastogenesis-related factors and raised BMD. Conclusion:MicroRNA-151a-3p could partly regulate osteoporosis by promoting osteoclast differentiation, and miRNA-151a-3p could be a potential therapeutic target for postmenopausal osteoporosis.

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“…For the ACS, an acute and severe cardiovascular disease, the medical treatment is difficult, its mortality is high, and its clinical manifestation and prognosis are very various, so early judgement for ACS prognosis is very important for the patients with ACS. The human OSCAR, a cell surface molecule, is involved in osteoclast differentiation and bone metabolism 6 . OSCAR may play an important role in vascular inflammation or plaque vulnerability during atherosclerosis 7 .…”

Section: Discussionmentioning

confidence: 99%

The predictive value of soluble osteoclast-associated receptor for the prognosis of acute coronary syndrome

Wang

Xie

et al. 2021

Sci Rep

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At present, prognostic biomarkers of acute coronary syndrome (ACS) are fewer. The aim of this study was to explore the predictive value of soluble osteoclast-associated receptor (sOSCAR) level for the major adverse cardiovascular events (MACE) occurring within 30 days after ACS. From January to August 2020, a total of 108 patients with ACS who were admitted to our hospital, were enrolled in this study. Of the 108 patients, 79 were men and 29 women. Patient-related data, including age, sex, body mass index, history of type 2 diabetes, history of hyperlipidemia and serum sOSCAR level, were collected. All patients were followed up for 30 days. Based on MACE occurrence, the 108 patients were divided into MACE group (n = 17) and non-MACE group (n = 91). The baseline data were compared between the two groups, MACE-independent risk factors were identified by multivariate regression analysis, and the predictive value of sOSCAR for MACE occurring within 30 days after CAS was analyzed using receiver operating characteristic (ROC) curve. At the same time, according to the type of ACS, the 108 patients with ACS were divided into unstable angina (UA) group (n = 29), non ST-segment elevation myocardial infarction (USTEMI) group (n = 45) and ST-segment elevation myocardial infarction (STEMI) group (n = 34), and then the sOSCAR level and MACE incidence were observed in each group. The serum sOSCAR level was significantly lower in the MACE group [130(100,183)] than in the non-MACE group [301(220,370)] (P = 0.000). The area under ROC curve of sOSCAR level for MACE occurring within 30 days after CAS was 0.860 with 95%CI 0.782–0.919, P < 0.001. Multivariate regression analysis indicated that the sOSCAR level was an independent risk factor for the MACE occurring within 30 days after CAS (OR 0.26, 95%CI 0.087–0.777, P = 0.04). The MACE incidence (0%) was the lowest but the sOSCAR level was the highest in the UA group, while in the STEMI group, the MACE incidence (23.53%) was the higest but the sOSCAR level was the lowest among the UA, STEMI and NSTEMI groups. Serum sOSCAR level may be used as a predictor of MACE occurring within the short-term after ACS. The higher the sOSCAR level, the lower the MACE incidence.

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Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression

Cited by 37 publications

References 48 publications

Leonurus�sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation

Leonurus�sibiricus L. ethanol extract promotes osteoblast differentiation and inhibits osteoclast formation

MicroRNA-151a-3p Functions in the Regulation of Osteoclast Differentiation: Significance to Postmenopausal Osteoporosis

The predictive value of soluble osteoclast-associated receptor for the prognosis of acute coronary syndrome

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