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Wnt-?-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage.

ABSTRACT: The aim of the present study was to determine the regulation of sclerostin (SOST) in osteoarthritis (OA) and its effect on articular cartilage degradation. Human cartilage samples from healthy and OA subjects were assessed by Safranin O staining and immunohistochemistry. Primary chondrocytes were pre?incubated with 250 ng/ml SOST, 10 ng/ml interleukin?1?? (IL?1?) or a combination of the two. The effects of treatment on the Wnt-?-catenin signaling pathway and cartilage degradation were examined by reverse transcription?quantitative polymerase chain reaction and western blotting. SOST was detected in the cartilage focal area, demonstrating secretion by osteocytes and chondrocytes. SOST has been identified to inhibit the Wnt-?-catenin signaling pathway by binding to low?density lipoprotein?related receptors 5 and 6, and catabolic factors were decreased in healthy chondrocytes. However, SOST did not influence human OA chondrocytes. IL?1? activated the Wnt-?-catenin signaling pathway and promoted cartilage degradation, which was inhibited by SOST in healthy and OA cartilage. The results of the present study suggested that SOST is important in maintaining the integrity of healthy, but not end?stage OA, cartilage.

SUBMITTER: Wu J

PROVIDER: S-EPMC5428759 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Wnt-β-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage.

Wu Jiang J Ma Long L Wu Long L Jin Qunhua Q

Molecular medicine reports 20170303 5

The aim of the present study was to determine the regulation of sclerostin (SOST) in osteoarthritis (OA) and its effect on articular cartilage degradation. Human cartilage samples from healthy and OA subjects were assessed by Safranin O staining and immunohistochemistry. Primary chondrocytes were pre‑incubated with 250 ng/ml SOST, 10 ng/ml interleukin‑1‑α (IL‑1α) or a combination of the two. The effects of treatment on the Wnt-β-catenin signaling pathway and cartilage degradation were examined b ...[more]

PMID: 28259981

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Project description:BackgroundThe serum levels of sclerostin (SOST) are significant elevated in patients with pathological cardiac remodeling after myocardial infarction (MI). However, the mechanisms of SOST in cardiac remodeling remain largely uncharacterized.MethodsCollecting patients with MI who presented with or without left ventricular (LV) remodeling, we investigated differences in SOST expression. The influence of overexpression and silenced of SOST on the angiogenesis of cardiac microvascular endothelial cells (CMECs) was explored through in vitro experiments, and the impact of SOST on Wnt signaling marker proteins was examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Finally, we observed the effects of SOST on cardiac function and morphology in mice MI model, and verified the role of the Wnt signaling marker proteins in vivo.ResultsSerum SOST was significantly increased in patients with cardiac remodeling. Increased SOST expression was also observed in the infarcted hearts of C57BL/6 mice that underwent ligation of the left anterior descending branch of the coronary artery to induce MI. Furthermore, loss and gain of function experiments were conducted to investigate the role of SOST in post-infarct cardiac remodeling in vivo and in vitro. Overexpression of SOST promoted the proliferation and migration of cardiac fibroblasts (CFs), and inhibited angiogenesis of CMECs. In addition, overexpressing SOST in mice significantly deteriorated the post-infarct cardiac remodeling, as shown by the increased LV end systolic and end diastolic dimensions, decreased ejection fraction, and increased myocyte cross-section area and myocardial fibrosis. However, suppressing SOST expression showed the opposite results. The expression of Wnt signaling marker proteins was inhibited after overexpression of SOST, and enhanced after suppression of SOST in vivo and in vitro, suggesting involvement of the Wnt signaling pathway.ConclusionsThe present study demonstrated that SOST aggravates post-infarct pathological myocardial remodeling by inhibiting angiogenesis of CMECs while promoting the proliferation of CFs, and this may be mediated by the Wnt signaling pathway. These results suggested that SOST might act as a biomarker to predict detrimental postinfarct cardiac remodeling, and may be a potential therapeutic target for the treatment of MI.

Dataset Information

Wnt-?-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage.

Publications

Wnt-β-catenin signaling pathway inhibition by sclerostin may protect against degradation in healthy but not osteoarthritic cartilage.

Similar Datasets

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