Activation of β‐catenin in <i>Col2</i>‐expressing chondrocytes leads to osteoarthritis‐like defects in hip joint

Xia, Chenjie; Wang, Pinger; Liang, Fang; Ge, Qinwen; Zou, Zhen; Dong, Rui; Zhang, Peng; Shi, Zhenyu; Xu, Rui; Zhang, Lei; Luo, Chen; Ying, Jun; Xiao, Lan; Shen, Jie; Chen, Di; Tong, Peijian; Jin, Hongting

doi:10.1002/jcp.28491

Cited by 19 publications

(13 citation statements)

References 38 publications

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“…Wnt signaling regulation of β-catenin plays critical role in variety of physiological processes (41). Previous studies have demonstrated that the expression level of β-catenin was upregulated in degenerative chondrocytes, resulting in loss of cartilage (42,43). In addition, conditional activation of β-catenin led to the abnormal differentiation of adult mouse chondrocytes and induced an OA-associated phenotype in mice (44).…”

Section: Discussionmentioning

confidence: 99%

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

et al. 2020

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Knee osteoarthritis (KOA) is a common joint disease with a high incidence rate among middle-aged and elderly individuals. However, the precise underlying pathological mechanisms and effective treatment of this disease remain to be determined. To explore the effect of high mobility group box 1 (HMGB1) on chondrocyte apoptosis and catabolism, the ATdc5 cell line was cultured as an in vitro model for cartilage research. cultured cells were treated with recombinant HMGB1 at different concentrations. Hoechst staining and flow cytometry demonstrated that HMGB1 administration significantly induced apoptosis of ATdc5 cells, which was the same as the effect of interleukin-1β treatment. HMGB1 also induced cartilage matrix degradation, as shown by Alcian blue staining. Moreover, HMGB1 markedly upregulated the expression levels of matrix metallopeptidases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (AdAMTS), while genetic silencing of HMGB1 significantly suppressed their expressions. The glycogen synthase kinase (GSK)-3β/β-catenin pathway was activated upon HMGB1 treatment. Pharmacological inhibitors or HMGB1 knockdown inactivated the GSK-3β/β-catenin pathway, inhibited the expression levels of downstream genes, including MMPs and AdAMTS, and attenuated the apoptosis of ATdc5 cells. Furthermore, the data demonstrated that HMGB1 promoted chondrocyte dysfunction via the regulation of estrogen sulfotransferase and Runt-related transcription factor 2. Thus, the findings of the present study demonstrated that HMGB1 induces chondrocyte cell apoptosis via activation of GSK-3β/β-catenin and the subsequent expression of multiple targeted genes.

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Section: Discussionmentioning

confidence: 99%

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

et al. 2020

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“…Then, we sought to clarify the combination of compounds in MYGY-Nb. UPLC/MS identified 16 major compounds of MYGY-Nb, in which kynylpinoside, rutinoside (Rutinos)_1, glycyrrhizin and glycyrrhetinic acid have been reported to have inhibitory effects on osteoclast formation (25)(26)(27)(28). Our future studies are warranted to investigate the anti-osteoporosis efficacy of these compounds in more detail.…”

Section: Discussionmentioning

confidence: 92%

“…The three-dimensional (3D) structure reconstruction of the distal femurs was performed using the NRecon software. The bone mineral density (BMD), trabecular separation (Tb.Sp, mm), trabecular number (Tb.N, 1/mm), trabecular thickness (Tb.Th, mm) and bone volume fraction (BV/TV, %) were analyzed as described previously (28).…”

Section: Micro-computed Tomography (Mct) Analysismentioning

confidence: 99%

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N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling

Zeng

Xu²,

Ling³

et al. 2022

Front. Endocrinol.

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Postmenopausal Osteoporosis (PMOP) is the most prevalent primary osteoporosis, attributable to an imbalance in osteoblast and osteoclast activity. Modified You-Gui-Yin (MYGY), a traditional Chinese herbal formula, is able to effectively treat PMOP, while the critical components and pharmacological mechanisms of MYGY are still unclear. In this study, we aimed to investigate the therapeutic effects and underlying mechanisms of N-butanol extract of MYGY (MYGY-Nb) in ovariectomized (OVX)-induced osteoporosis mice. Histological staining and micro-computed tomography (μCT) analysis showed that MYGY-Nb was more effective in the suppression of OVX-induced bone loss than MYGY original formula. Subsequently, liquid chromatography and mass spectrometry analysis identified 16 critical compounds of MYGY-Nb and some of them are reported to affect osteoclast functions. Furthermore, in vivo and in vitro experiments demonstrated that MYGY-Nb significantly attenuated osteoclastogenesis by down-regulating RANKL-mediated NF-κB signaling. In conclusion, our study indicated that MYGY-Nb suppresses NF-κB signaling and osteoclast formation to mitigate bone loss in PMOP, implying that MYGY-Nb and its compounds are potential candidates for development of anti-PMOP drugs.

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“…Th, mm), average trabecular separation (Tb. Sp, mm) and bone mineral density (BMD) was calculated as previously described 16 .…”

Section: Micro-ct Analysismentioning

confidence: 99%

Exploring the mechanism of Bushenhuoxue formula acting on postmenopausal osteoporosis via network pharmacology and experimental validation

Wang²,

He³

et al. 2021

Preprint

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Background: Bushenhuoxue (BSHX) formula, a ten-compound herbal decoction, has been used to treat postmenopausal osteoporosis (PMOP) in China for decades. Our previous study also revealed the anti-PMOP effects of BSHX formula in ovariectomized (OVX) mice. However, its pharmacological mechanisms remain unknown. Methods: Network pharmacology followed by animal experiments was used to explore the action mechanism of BSHX formula. Firstly, we obtained the chemical compounds and potential targets of BSHX formula using TCMSP and TCMID databases. Simultaneously, GeneCards and DisGeNET databases were used to determine the targets in PMOP. Based on their overlapping genes between BSHX formula and PMOP, a protein-protein interaction (PPI) network was constructed for screening hub-targets. GO and KEGG enrichment analyses were further performed to identify the critical biological processes and signaling pathways. In vivo experimental study, an OVX mouse model was established to determine the anti-PMOP effects of BSHX formula via Micro-CT assay and ABH staining. The expressions of β-catenin, alkaline phosphatase (ALP), vascular endothelial growth factor (VEGF) and CD31 were detected by immunohistochemistry.Results: A total of 218 active ingredients and 274 related targets were identified in BSHX formula. After matching with 292 therapeutic targets of PMOP, 64 overlapping genes were obtained and further used to build a PPI network in which CTNNB1 and VEGFA played a central role. GO and KEGG enrichment analyses indicated that the anti-PMOP effects of BSHX formula were mainly associated with cell proliferation, angiogenesis and their regulated pathways including β-catenin signaling and VEGF signaling. In mouse experiments, we revealed that bone mass and blood vessels in the OVX mice were significantly enhanced after treated with BSHX formula for 8 weeks. Moreover, down-regulations of β-catenin, ALP, VEGF and CD31 caused by OVX surgery were significantly restored by BSHX formula.Conclusions: Through network pharmacology and an experimental validation, we have revealed that BSHX formula exerts anti-PMOP effects mainly through promoting β-catenin-mediated osteogenesis and VEGF-mediated angiogenesis. BSHX formula can be considered as a new option for the treatment of PMOP.

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Activation of β‐catenin in Col2‐expressing chondrocytes leads to osteoarthritis‐like defects in hip joint

Cited by 19 publications

References 38 publications

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

The GSK‑3β/β‑catenin signaling pathway is involved in HMGB1‑induced chondrocyte apoptosis and cartilage matrix degradation

N-Butanol Extract of Modified You-Gui-Yin Attenuates Osteoclastogenesis and Ameliorates Osteoporosis by Inhibiting RANKL-Mediated NF-κB Signaling

Exploring the mechanism of Bushenhuoxue formula acting on postmenopausal osteoporosis via network pharmacology and experimental validation

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