Pcsk9 Knockout Aggravated Experimental Apical Periodontitis via LDLR

2021 ◽  
pp. 002203452110151
Author(s):  
L. Huang ◽  
H. Wu ◽  
Y. Wu ◽  
F. Song ◽  
L. Zhang ◽  
...  
Keyword(s):  
Osteoclast Differentiation ◽  
Apical Periodontitis ◽  
Cholesterol Homeostasis ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Lps Challenge ◽  
Tnf Α ◽  
Computed Tomography Scanning

Apical periodontitis (AP), an inflammatory lesion around the apex of tooth roots, is mostly caused by dental pulp infection. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a vital role in regulating cholesterol homeostasis by targeting low-density lipoprotein receptor (LDLR) and participates in bacterium-induced chronic periodontitis. However, the roles of PCSK9 in AP are unknown. Here, we investigated its role in AP by using Pcsk9−/− mice. Micro–computed tomography scanning and histological staining revealed that the periapical bone loss of Pcsk9−/− mice was greater than that of wild-type (WT) mice, and increased expression of inflammation-related factors tumor necrosis factor α (TNF-α) and interleukin (IL)–6 was also observed. Immunofluorescence staining and quantitative real-time polymerase chain reaction showed PCSK9 expression in bone marrow macrophages (BMMs) was increased after treatment with lipopolysaccharide (LPS). This finding was consistent with the in vivo results that the expression level of PCSK9 in exposed WT mice increased compared with that in unexposed WT mice. After LPS challenge, the expression levels of TNF-α, IL-1β, and IL-6 in BMMs were increased, and Pcsk9 knockout aggravated the expression of these inflammatory factors. The number of osteoclasts positive for tartrate-resistant acid phosphatase staining around the apical lesion in Pcsk9−/− mice was higher than that in WT mice. Then BMMs underwent the osteoclast differentiation. Pcsk9 knockout BMMs induced increased and larger osteoclasts. While this effect of Pcsk9 knockout was abolished by the addition of Ldlr small interfering RNA, revealing that Pcsk9 knockout increased osteoclastogenesis was dependent on the LDLR. Immunohistochemistry staining showed increased expression level of LDLR in exposed Pcsk9−/− periapical areas. In vitro experiments showed that LPS promoted the expression level of LDLR in Pcsk9−/− BMMs and increased osteoclast formation ability, indicating that LPS promoted the elevation of osteoclasteogenesis caused by the Pcsk9 knockout. In conclusion, Pcsk9 deficiency aggravated the inflammatory response and promoted the osteoclastogenesis in an LDLR-dependent manner in AP experimental mice.

scholarly journals Decitabine Inhibits Bone Resorption in Periodontitis by Upregulating Anti-Inflammatory Cytokines and Suppressing Osteoclastogenesis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 199
Author(s):  
Urara Tanaka ◽  
Shunichi Kajioka ◽  
Livia S. Finoti ◽  
Daniela B. Palioto ◽  
Denis F. Kinane ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Bone Resorption ◽  
Bone Loss ◽  
Inflammatory Cytokines ◽  
Osteoclast Differentiation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Osteoblastic Cell Line ◽  
Anti Inflammatory

DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg/day) or vehicle treatment. We evaluated bone resorption, osteoclast differentiation by tartrate-resistant acid phosphatase (TRAP) and mRNA expression of anti-inflammatory molecules using cluster differentiation 14 positive (CD14+) monocytes from human peripheral blood. Our data showed that decitabine inhibited bone loss and osteoclast differentiation experimental periodontitis, and suppressed osteoclast CD14+ human monocytes; and conversely, that it increased bone mineralization in osteoblastic cell line MC3T3-E1 in a concentration-dependent manner. In addition to increasing IL10 (interleukin-10), TGFB (transforming growth factor beta-1) in CD14+ monocytes, decitabine upregulated KLF2 (Krüppel-like factor-2) expression. Overexpression of KLF2 protein enhanced the transcription of IL10 and TGFB. On the contrary, site-directed mutagenesis of KLF2 binding site in IL10 and TFGB abrogated luciferase activity in HEK293T cells. Decitabine reduces bone loss in a mouse model of periodontitis by inhibiting osteoclastogenesis through the upregulation of anti-inflammatory cytokines via KLF2 dependent mechanisms. DNA methyltransferase inhibitors merit further investigation as a possible novel therapy for periodontitis.

scholarly journals Protective Effect of Phillyrin on Lethal LPS-Induced Neutrophil Inflammation in Zebrafish

2017 ◽  
Vol 43 (5) ◽  
pp. 2074-2087 ◽  
Author(s):  
Liling Yang ◽  
Xiangjun Zhou ◽  
Weijuan Huang ◽  
Qin Fang ◽  
Jianlan Hu ◽  
...  
Keyword(s):  
Signalling Pathway ◽  
Dependent Manner ◽  
Zebrafish Model ◽  
Lps Challenge ◽  
Cell Counts ◽  
Tnf Α ◽  
Forsythia Suspensa ◽  
Anti Inflammatory

Background/Aims: Forsythia suspensa Vahl. (Oleaceae) fruits are widely used in traditional Chinese medicine to treat pneumonia, typhoid, dysentery, ulcers and oedema. Antibacterial and anti-inflammatory activities have been reported for phillyrin (PHN), the main ingredient in Forsythia suspensa Vahl fruits, in vitro. However, the underlying mechanisms in vivo remain poorly defined. In this study, we discovered that PHN exerted potent anti-inflammatory effects in lethal LPS-induced neutrophil inflammation by suppressing the MyD88-dependent signalling pathway in zebrafish. Methods: LPS-yolk microinjection was used to induce a lethal LPS-infected zebrafish model. The effect of PHN on the survival of zebrafish challenged with lethal LPS was evaluated using survival analysis. The effect of PHN on neutrophil inflammation grading in vivo was assessed by tracking neutrophils with a transgenic line. The effects of PHN on neutrophil production and migration were analysed by SB+ cell counts during consecutive hours after modelling. Additionally, key cytokines and members of the MyD88 signalling pathway that are involved in inflammatory response were detected using quantitative RT-PCR. To assess gene expression changes during consecutive hours after modelling, the IL-1β, IL-6, TNF-α, MyD88, TRIF, ERK1/2, JNK, IκBa and NF-κB expression levels were measured. Results: PHN could protect zebrafish against a lethal LPS challenge in a dose-dependent manner, as indicated by decreased neutrophil infltration, reduced tissue necrosis and increased survival rates. Up-regulated IL-1β, IL-6 and TNF-α expression also showed the same tendencies of depression by PHN. Critically, PHN significantly inhibited the LPS-induced activation of MyD88, IκBa, and NF-κB but did not affect the expression of ERK1/2 MAPKs or JNK MAPKs in LPS-stimulated zebrafish. Additionally, PHN regulated the MyD88/IκBα/NF-κB signalling pathway by controlling IκBα, IL-1β, IL-6, and TNF-α expression. Conclusion: This study provides a rationale for the clinical application of PHN as an anti-inflammatory agent.

scholarly journals Promotion of osteoclastogenesis by IL-26 in rheumatoid arthritis

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Kyung-Ann Lee ◽  
Kyoung-Woon Kim ◽  
Bo-Mi Kim ◽  
Ji-Yeon Won ◽  
Hong Ki Min ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Peripheral Blood ◽  
Osteoclast Differentiation ◽  
Joint Damage ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Receptor Subunit ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes

Abstract Background The inflammatory cascade in the rheumatoid arthritis (RA) synovium is modulated by a variety of cytokine and chemokine networks; however, the roles of IL-26, in RA pathogenesis, are poorly defined. Here, we investigated the functional role of interleukin-26 (IL)-26 in osteoclastogenesis in RA. Methods We analyzed levels of IL-20 receptor subunit A (IL-20RA), CD55, and receptor activator of nuclear factor kappaB (NF-κB) ligand (RANKL) in RA fibroblast-like synoviocytes (FLSs) using confocal microscopy. Recombinant human IL-26-induced RANKL expression in RA-FLSs was examined using real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Human peripheral blood monocytes were cultured with macrophage colony-stimulating factor (M-CSF) and IL-26, after which osteoclastogenesis was evaluated by counting the number of tartrate-resistant acid phosphatase-positive multinucleated cells. Additionally, osteoclastogenesis was evaluated by monocytes co-cultured with IL-26-prestimulated FLSs. Results The expression of IL-20RA in RA-FLSs was higher than that in osteoarthritis-FLSs. Additionally, in IL-26-pretreated RA-FLSs, the expression of IL-20RA (but not IL-10 receptor subunit B) and RANKL increased in a dose-dependent manner, with IL-26-induced RANKL expression reduced by IL-20RA knockdown. Moreover, IL-26-induced RANKL expression was significantly downregulated by inhibition of signal transducer and activator of transcription 1, mitogen-activated protein kinase, and NF-κB signaling. Furthermore, IL-26 promoted osteoclast differentiation from peripheral blood monocytes in the presence of low dose of RANKL, with IL-26 exerting an additive effect. Furthermore, co-culture of IL-26-pretreated RA-FLSs with peripheral blood monocytes also increased osteoclast differentiation in the absence of addition of RANKL. Conclusions IL-26 regulated osteoclastogenesis in RA through increased RANKL expression in FLSs and direct stimulation of osteoclast differentiation. These results suggest the IL-26/IL-20RA/RANKL axis as a potential therapeutic target for addressing RA-related joint damage.

scholarly journals CD14+CD16− monocytes are the main precursors of osteoclasts in rheumatoid arthritis via expressing Tyro3TK

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Jimeng Xue ◽  
Liling Xu ◽  
Huaqun Zhu ◽  
Mingxin Bai ◽  
Xin Li ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Tyrosine Kinase ◽  
Osteoclast Differentiation ◽  
Tender Joint Count ◽  
Tartrate Resistant Acid Phosphatase ◽  
Dependent Manner ◽  
Monocyte Subsets ◽  
Tender Joint ◽  
Critical Signal

Abstract Background Monocytes as precursors of osteoclasts in rheumatoid arthritis (RA) are well demonstrated, while monocyte subsets in osteoclast formation are still controversial. Tyro3 tyrosine kinase (Tyro3TK) is a member of the receptor tyrosine kinase family involved in immune homeostasis, the role of which in osteoclast differentiation was reported recently. This study aimed to compare the osteoclastic capacity of CD14+CD16+ and CD14+CD16− monocytes in RA and determine the potential involvement of Tyro3TK in their osteoclastogenesis. Methods Osteoclasts were induced from CD14+CD16+ and CD14+CD16− monocyte subsets isolated from healthy control (HC) and RA patients in vitro and evaluated by tartrate-resistant acid phosphatase (TRAP) staining. Then, the expression of Tyro3TK on CD14+CD16+ and CD14+CD16− monocyte subsets in the peripheral blood of RA, osteoarthritis (OA) patients, and HC were evaluated by flow cytometry and qPCR, and their correlation with RA patient clinical and immunological features was analyzed. The role of Tyro3TK in CD14+CD16− monocyte-mediated osteoclastogenesis was further investigated by osteoclast differentiation assay with Tyro3TK blockade. Results The results revealed that CD14+CD16− monocytes were the primary source of osteoclasts. Compared with HC and OA patients, the expression of Tyro3TK on CD14+CD16− monocytes in RA patients was significantly upregulated and positively correlated with the disease manifestations, such as IgM level, tender joint count, and the disease activity score. Moreover, anti-Tyro3TK antibody could inhibit Gas6-mediated osteoclast differentiation from CD14+CD16− monocytes in a dose-dependent manner. Conclusions These findings indicate that elevated Tyro3TK on CD14+CD16− monocytes serves as a critical signal for osteoclast differentiation in RA.

Spatholobus suberectus Inhibits Osteoclastogenesis and Stimulates Chondrogenesis

2014 ◽  
Vol 42 (05) ◽  
pp. 1123-1138 ◽  
Author(s):  
Nam-Kyung Im ◽  
Sung-Gyu Lee ◽  
Dong-Sung Lee ◽  
Pil-Hoon Park ◽  
In-Seon Lee ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Osteoclast Differentiation ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Chondral Defect ◽  
Active Components ◽  
Tnf Α ◽  
Receptor Activator ◽  
The Matrix ◽  
Spatholobus Suberectus

This study was carried out to investigate the effect of Spatholobus suberectus Dunn (SS) on the protection of chondral defect and inhibition of osteoclastogenesis. To examine these effects, we measured the matrix metalloproteinase (MMP) levels in SW1353 chondrosarcoma cells and performed tartrate-resistant acid phosphatase (TRAP) staining in bone marrow macrophage (BMM)-derived osteoclasts. To investigate the anti-osteoarthritis (OA) effects, we assessed TNF-α-induced MMP-1, -3, -9 and tissue inhibitors of matrix metalloproteinase (TIMP) expression levels in SW1353 cells. We observed that SS extract significantly inhibited MMP and TIMP expression in SW1353 cells. Also, SS extract inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. These results suggest that SS extract may have a potential in the treatment of bone loss and chondral defect by suppressing osteoclast differentiation and decreasing the expression of OA factors. Therefore, clarification of the mechanism of the action of SS extract and its active components is needed.

Nickel-refining dust regulates the expression of inflammatory factors in NIH/3T3 cells

2019 ◽  
Vol 35 (3) ◽  
pp. 239-247 ◽  
Author(s):  
Runan Qin ◽  
Yue Wang ◽  
Shengyuan Wang ◽  
Bing Xia ◽  
Rui Xin ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Dependent Manner ◽  
3T3 Cells ◽  
Related Factors ◽  
Experimental Conditions ◽  
Tnf Α ◽  
Cox 2 ◽  
Nih 3T3 ◽  
Nih 3T3 Cells

Nickel (Ni) is a metal known to be a human carcinogen that occupational workers can be exposed to during the process of Ni refining. We investigated the molecular mechanism of inflammation that is induced by Ni-refining dust in a factory, using concentrations of 0, 25, 50, and 100 µg/mL for 24 h and 48 h, in vitro. Quantitative real-time polymerase chain reactions (qRT-PCR), Western blot analysis, and enzyme-linked immunosorbent assays (ELISA) were used to detect the transcriptional expression levels of nuclear factor-κB (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). Results showed that Ni-refining dust decreased the secretion of IL-6 under the experimental conditions. In contrast, Ni-refining dust activated NF-κB expression and stimulated the secretion of TNF-α, IL-1β, iNOS, and COX-2 in a dose- and time-dependent manner. To summarize, we demonstrated that exposure to Ni-refining dust can induce the expression of NF-κB in NIH/3T3 cells and the secretion of inflammation related factors. This provides a new basis for further study of the inflammatory effects of Ni-refining dust.

Effects of Irbesartan on Phenotypic Alteration of Monocyte and Inflammatory Status of Hypertensive Patients with Left Ventricular Hypertrophy

2021 ◽  
Author(s):  
Jingsi Zhang ◽  
Lina Yang ◽  
Yanchun Ding
Keyword(s):  
Ventricular Hypertrophy ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Left Ventricular ◽  
Inflammatory Factors ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Hypertensive Patients ◽  
Inflammatory Status ◽  
Tnf Α

Abstract Background: Circulating monocytes and tissue macrophages play complex roles in pathogenesis of hypertension and its target organ damage. In this study we observed the alterations of monocyte phenotype and inflammatory state of hypertensive patients with left ventricular hypertrophy (LVH) and the effects of Irbesartan on it. We explored new mechanisms of Irbesartan to reverse LVH and provided new targets for the prevention and treatment of hypertensive target organ damage.Methods: The CD163 and CD206 expressions on monocytes were detected as well as the IL-10 and TNF-α levels in serum of hypertensive patients with or without LVH and healthy volunteers. Furthermore, we treated monocytes of LVH group with different concentrations of Irbesartan, and then CD163, CD206, IL-10 and TNF-α were detected. Results: We found for the first time that the expression of CD163, CD206 and IL-10 of LVH group was lower than that of non-LVH group and healthy control, but the TNF-α level of LVH group was significantly higher. Irbesartan could upregulate the expression of CD163 and CD206 of hypertensive patients with LVH in a concentration-dependent manner. Irbesartan could also increase the expression of IL-10 and inhibit the expression of TNF-α in monocytes culture supernatant in a concentration-dependent manner. Conclusions: Our data suggests that inflammation was activated in hypertensive patients with LVH, the monocyte phenotype was mainly pro-inflammatory. The expression of pro-inflammatory factors increased while the expression of anti-inflammatory factors decreased. Irbesartan could alter monocyte phenotype and inflammatory status in hypertensive patients with LVH, which may be a new mechanism of Irbesartan to reverse LVH.Trail registration: The study protocols were approved by the Ethical Committee of the Second Affiliated Hospital of Dalian Medical University. Each patient signed the informed consent.

scholarly journals BCPA {N,N′-1,4-Butanediylbis[3-(2-chlorophenyl)acrylamide]} Inhibits Osteoclast Differentiation through Increased Retention of Peptidyl-Prolyl cis-trans Isomerase Never in Mitosis A-Interacting 1

2018 ◽  
Vol 19 (11) ◽  
pp. 3436 ◽  
Author(s):  
Eugene Cho ◽  
Jin-Kyung Lee ◽  
Jee-Young Lee ◽  
Zhihao Chen ◽  
Sun-Hee Ahn ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Transmembrane Protein ◽  
Osteoclast Differentiation ◽  
Osteoclast Formation ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
And Function

Osteoporosis is caused by an imbalance of osteoclast and osteoblast activities and it is characterized by enhanced osteoclast formation and function. Peptidyl-prolyl cis-trans isomerase never in mitosis A (NIMA)-interacting 1 (Pin1) is a key mediator of osteoclast cell-cell fusion via suppression of the dendritic cell-specific transmembrane protein (DC-STAMP). We found that N,N′-1,4-butanediylbis[3-(2-chlorophenyl)acrylamide] (BCPA) inhibited receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis in a dose-dependent manner without cytotoxicity. In addition, BCPA attenuated the reduction of Pin1 protein during osteoclast differentiation without changing Pin1 mRNA levels. BCPA repressed the expression of osteoclast-related genes, such as DC-STAMP and osteoclast-associated receptor (OSCAR), without altering the mRNA expression of nuclear factor of activated T cells (NFATc1) and cellular oncogene fos (c-Fos). Furthermore, Tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells were significantly decreased by BCPA treatment compared to treatment with the Pin1 inhibitor juglone. These data suggest that BCPA can inhibit osteoclastogenesis by regulating the expression of the DC-STAMP osteoclast fusion protein by attenuating Pin1 reduction. Therefore, BCPA may be used to treat osteoporosis.

scholarly journals Inhibitory Effects of 2N1HIA (2-(3-(2-Fluoro-4-Methoxyphenyl)-6-Oxo-1(6H)-Pyridazinyl)-N-1H-Indol-5-Ylacetamide) on Osteoclast Differentiation via Suppressing Cathepsin K Expression

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3139 ◽  
Author(s):  
Sun-Hee Ahn ◽  
Zhihao Chen ◽  
Jinkyung Lee ◽  
Seok-Woo Lee ◽  
Sang Min ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Osteoclast Differentiation ◽  
Cell Formation ◽  
Cathepsin K ◽  
Bone Diseases ◽  
Specific Gene ◽  
Tartrate Resistant Acid Phosphatase ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Gene Markers

Osteoclasts are large multinucleated cells which are induced by the regulation of the receptor activator of nuclear factor kappa-Β ligand (RANKL), which is important in bone resorption. Excessive osteoclast differentiation can cause pathologic bone loss and destruction. Numerous studies have targeted molecules inhibiting RANKL signaling or bone resorption activity. In this study, 11 compounds from commercial libraries were examined for their effect on RANKL-induced osteoclast differentiation. Of these compounds, only 2-(3-(2-fluoro-4-methoxyphenyl)-6-oxo-1(6H)-pyridazinyl)-N-1H-indol-5-ylacetamide (2N1HIA) caused a significant decrease in multinucleated tartrate-resistant acid phosphatase (TRAP)-positive cell formation in a dose-dependent manner, without inducing cytotoxicity. The 2N1HIA compound neither affected the expression of osteoclast-specific gene markers such as TRAF6, NFATc1, RANK, OC-STAMP, and DC-STAMP, nor the RANKL signaling pathways, including p38, ERK, JNK, and NF-κB. However, 2N1HIA exhibited a significant impact on the expression levels of CD47 and cathepsin K, the early fusion marker and critical protease for bone resorption, respectively. The activity of matrix metalloprotease-9 (MMP-9) decreased due to 2N1HIA treatment. Accordingly, bone resorption activity and actin ring formation decreased in the presence of 2N1HIA. Taken together, 2N1HIA acts as an inhibitor of osteoclast differentiation by attenuating bone resorption activity and may serve as a potential candidate in preventing and/or treating osteoporosis, or other bone diseases associated with excessive bone resorption.

scholarly journals The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yangyang Li ◽  
Yongfeng Zhang ◽  
Weiqi Meng ◽  
Yutong Li ◽  
Tao Huang ◽  
...  
Keyword(s):  
Trabecular Bone ◽  
Bone Morphogenetic Protein ◽  
Type I Collagen ◽  
Osteoclast Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Inflammatory Factors ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Serum Concentrations ◽  
Morphogenetic Protein

Yishen Bugu Ye (YSBGY), a traditional Chinese medicine comprising 12 types of medicinal herbs, is often prescribed in China to increase bone strength. In this study, the antiosteoporotic effects of YSBGY were investigated in C57BL/6 mice afflicted with dexamethasone- (Dex-) induced osteoporosis (OP). The results showed that YSBGY reduced the interstitial edema in the liver and kidney of mice with Dex-induced OP. It also increased the number of trabecular bone elements and chondrocytes in the femur, promoted cortical bone thickness and trabecular bone density, and modulated the OP-related indexes in the femur and tibia of OP mice. It also increased the serum concentrations of type I collagen, osteocalcin, osteopontin, bone morphogenetic protein-2, bone morphogenetic protein receptor type 2, C-terminal telopeptide of type I collagen, and runt-related transcription factor-2 and reduced those of tartrate-resistant acid phosphatase 5 and nuclear factor of activated T cells in these mice, suggesting that it improved osteoblast differentiation and suppressed osteoclast differentiation. The anti-inflammatory effect of YSBGY was confirmed by the increase in the serum concentrations of interleukin- (IL-) 33 and the decrease in concentrations of IL-1, IL-7, and tumor necrosis factor-α in OP mice. Furthermore, YSBGY enhanced the serum concentrations of superoxide dismutase and catalase in these mice, indicating that it also exerted antioxidative effects. This is the first study to confirm the antiosteoporotic effects of YSBGY in mice with Dex-induced OP, and it showed that these effects may be related to the YSBGY-induced modulation of the osteoblast/osteoclast balance and serum concentrations of inflammatory factors. These results provide experimental evidence supporting the use of YSBGY for supporting bone formation in the clinical setting.

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