Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Zhang, Hao; Wang, Lipeng; Cui, Jin; Wang, Sicheng; Han, Yafei; Shao, Hongda; Wang, Cheng; Yan, Hu; Li, Xiaoqun; Zhou, Qirong; Guo, Jiawei; Xinchen, Zhuang; Sheng, Shihao; Zhang, Tao; Zhou, Dongyang; Chen, Jiao; Wang, Fuxiao; Gao, Qianmin; Jing, Yingying; Chen, Xiao; Su, Jiacan

doi:10.1101/2022.03.17.484053

Cited by 11 publications

(13 citation statements)

References 65 publications

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“…Osteoarthritis (OA) is a widespread irreversible articular disease marked by articular cartilage deterioration and subsequent osteophytes. 1,2 It affects millions of people worldwide, especially older people over 60 years old. 3 The current mainstream OA treatment options fall into three categories: physical therapy, pharmacotherapy and surgery.…”

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confidence: 99%

Endothelial Stat3 activation promotes osteoarthritis development

Zhang

Liu

et al. 2023

Cell Proliferation

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The mechanism of the balance between subchondral angiogenesis and articular damage within osteoarthritis (OA) progression remains a mystery. However, the lack of specific drugs leads to limited clinical treatment options for OA, frequently failing to prevent eventual joint destruction in patients. Increasing evidence suggests that subchondral bone angiogenesis precedes cartilage injury, while proliferating endothelial cells (ECs) induce abnormal bone formation. Signal transducer and activator of transcription 3 (Stat3) is triggered by multiple cytokines in the OA microenvironment. Here, we observed elevated Stat3 activation in subchondral bone H‐type vessels. Endothelial Stat3 activation will lead to stronger cell proliferation, migration and angiogenesis by simulating ECs in OA. In contrast, either Stat3 activation inhibition or knockdown of Stat3 expression could relieve such alterations. More interestingly, blocking Stat3 in ECs alleviated angiogenesis‐mediated osteogenic differentiation and chondrocyte lesions. Stat3 inhibitor reversed surgically induced subchondral bone H‐type vessel hyperplasia in vivo, significantly downregulating vessel volume and vessel number. Due to the reduced angiogenesis, subchondral bone deterioration and cartilage loss were alleviated. Overall, our data suggest that endothelial Stat3 activation is an essential trigger for OA development. Therefore, targeted Stat3 blockade is a novel promising therapeutic regimen for OA.

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confidence: 99%

Endothelial Stat3 activation promotes osteoarthritis development

Zhang

Liu

et al. 2023

Cell Proliferation

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“…The results of KEGG analysis showed that RJNTF could treat KOA by interfering with multiple signaling pathways such as NF-κB, apoptosis, HIF-1 signaling pathway, JAT-STAT signaling pathway and IL-17 signaling pathway (Fig. 2B) (31)(32)(33)(34).…”

Section: Resultsmentioning

confidence: 99%

Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis

Chen,

Zhang,

Luo

et al. 2024

Mol Med Rep

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Knee osteoarthritis (KOA) is a chronic degenerative disease that affects the quality of life of middle-aged and elderly individuals, and is one of the major factors leading to disability. Rongjin Niantong Fang (RJNTF) can alleviate the clinical symptoms of patients with KOA, but the molecular mechanism underlying its beneficial effects on KOA remains unknown. Using pharmacological analysis and in vitro experiments, the active components of RJNTF were analyzed to explore their potential therapeutic targets and mechanisms in KOA. The potential targets and core signaling pathways by which RJNTF exerts its effects on KOA were obtained from databases such as Gene Expression Omnibus, Traditional Chinese Medicine Systems Pharmacology and Analysis Platform. Subsequently, chondrocyte apoptosis was modeled using hydrogen peroxide (H 2 O 2 ). Cell Counting Kit-8 assay involving a poly [ADP-ribose] polymerase-1 (PARP1) inhibitor, DAPI staining, reverse transcription-quantitative PCR, Annexin V-FITC/PI staining and flow cytometry, western blotting and co-immunoprecipitation analysis were used to determine the therapeutic efficacy of RJNTF on KOA and to uncover the molecular mechanism. It was found that PARP1-knockdown lentivirus, incubation with PARP1 inhibitor PJ34, medium and high doses of RJNTF significantly reduced H 2 O 2 -induced chondrocyte apoptosis. Medium and high doses of RJNTF downregulated the expression of cleaved caspase-3, cleaved PARP1 and PAR total proteins, as well as nucleus proteins of apoptosis-inducing factor (AIF) and migration inhibitory factor (MIF), and upregulated the expression of caspase-3, PARP1 total protein, as well as the cytoplasmic expression of AIF and MIF, suggesting that RJNTF may inhibit chondrocyte apoptosis through the PARP1/AIF signaling pathway.

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“…At the same time the ML model results are con rmed by classical statistics, correlation analysis, whereas the literature data are contradictory. Different studies consider high or low pancreatic duct diameter as risk factors; the observations on BMI and surgical technics are controversial in general [10,15,39]. Being important for ML models development, BMI was not correlated with pancreatic stulas development.…”

Section: Discussionmentioning

confidence: 98%

Machine learning approach in diagnosis and risk factors detection of pancreatic fistula

Potievskiy,

Petrov,

Ivanov

et al. 2024

Preprint

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Introduction: The aim of the study was to develop a predictive ML model for postoperative pancreatic fistula and to determine the main risk factors of the complication. Materials and Methods: We performed a single-centre retrospective clinical study. 150 patients, who underwent pancreatoduodenal resection in FSBI NMRRC, were included. We developed ML models of biochemic leak and fistula B/C development. Logistic regression, Random forest and CatBoost algorithms were employed. The risk factors were evaluated basing on the most accurate model, roc auc, and Kendall correlation, p<0.05. Results: We detected a significant positive correlation between blood and drain amylase level increase in association with biochemical leak and fistula B/C. The CatBoost algorithm was the most accurate, roc auc 74%-86%. The main pre- and intraoperative prognostic factors of all the fistulas were tumor vascular invasion, age and BMI, roc auc 70%. Specific fistula B/C factors were the same. Basing on the 3-5 days data, biochemical leak and fistula B/C risk factors were blood and drain amylase levels, blood leukocytes, roc auc 86% and 75 %. Conclusion: We developed sufficient quality ML models of postoperative pancreatic fistulas. Blood and drain amylase level increase, tumor vascular invasion, age and BMI were the major risk factors of further fistula B/C development.

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Maintaining hypoxia environment of subchondral bone alleviates osteoarthritis progression

Cited by 11 publications

References 65 publications

Endothelial Stat3 activation promotes osteoarthritis development

Endothelial Stat3 activation promotes osteoarthritis development

Network pharmacology combined with experimental validation to investigate the effect of Rongjin Niantong Fang on chondrocyte apoptosis in knee osteoarthritis

Machine learning approach in diagnosis and risk factors detection of pancreatic fistula

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