Home Exome pubmed: wnt1 <em>SIRT2</em> Alleviates Inflammatory Response, Apoptosis, and ECM Degradation in Osteoarthritic Chondrocytes by Stabilizing <em>PCK1</em>

<em>SIRT2</em> Alleviates Inflammatory Response, Apoptosis, and ECM Degradation in Osteoarthritic Chondrocytes by Stabilizing <em>PCK1</em>

pubmed: wnt1 2024-12-11

Discov Med. 2024 Oct;36(189):2046-2054. doi: 10.24976/Discov.Med.202436189.188.

ABSTRACT

BACKGROUND: It has been reported that Sirtuin 2 (SIRT2) prevents phosphoenolpyruvate carboxykinase 1 (PCK1) degradation, which can be involved in aging-induced osteoarthritis (OA), but the molecular mechanism of SIRT2/PCK1 in chondrocytes has not been clarified. Therefore, this study aims to explore the mechanism of SIRT2/PCK1 in chondrocyte inflammation.

METHOD: To establish the OA model in vitro, chondrocytes cultured with interleukin-1β (IL-1β, 10 ng/mL) and manipulation of SIRT2 and PCK1 expression in the constructed cells to elucidate the interaction between the two genes. 1,9-Dimethyl-Methylene Blue (DMMB) was used to detect cellular glycosaminoglycan (GAG) content. Inflammatory factor levels were assessed using Enzyme-linked Immunosorbent Assay (ELISA). Apoptosis was detected by osmotic dye. The expression of B-cell lymphoma-2 (Bcl-2), Bcl-2 Associated X (Bax), Wnt Family Member 1 (Wnt1), catenin Beta 1 (β-catenin), Aggrecan, Collagen II, matrix metallopeptidase 13 (MMP-13) proteins in cells were analyzed using Western blot.

RESULTS: PCK1 gained lower expressions in OA cell models. Overexpression of PCK1 or SIRT2 in the IL-1β chondrocyte model of inflammation promoted GAG content, inhibited apoptosis and Wnt/β-catenin protein expression, and lowered the levels of inflammatory factors. PCK1 silencing was proved to have the opposite effect. SIRT2 overexpression rescued the increased inflammation, MMP-13 expression, and apoptosis and the decreased Aggrecan and Collagen II expression caused by PCK1 silencing. PCK1 silencing also reversed the positive effects of SIRT2 overexpression on chondrocytes.

CONCLUSION: SIRT2 inhibits articular chondrocyte extracellular matrix (ECM) degradation, inflammatory factor expression, and apoptosis via PCK1.

PMID:39463224 | DOI:10.24976/Discov.Med.202436189.188