| First Author | Zhou Y | Year | 2023 |
| Journal | Eur J Med Res | Volume | 28 |
| Issue | 1 | Pages | 332 |
| PubMed ID | 37689723 | Mgi Jnum | J:353973 |
| Mgi Id | MGI:7718758 | Doi | 10.1186/s40001-023-01267-4 |
| Citation | Zhou Y, et al. (2023) Impaired autophagy contributes to the aggravated deterioration of osteoarthritis articular cartilage by peroxisome proliferator-activated receptor alpha deficiency, associated with decreased ERK and Akt activation. Eur J Med Res 28(1):332 |
| abstractText | BACKGROUND: Although the chondroprotection of peroxisome proliferator-activated receptor alpha (PPARalpha) activation against osteoarthritis (OA) has been revealed, the regulatory mechanism of PPARalpha deficiency to aggravate osteoarthritic cartilage deterioration remains unclear. Here, we aimed to investigate whether and how autophagy is involved in OA pathological progression. METHODS: Model of experimental OA was established using destabilization of the medial meniscus in PPARalpha-KO 129S4/SvJae male mice, followed by histopathological detection of articular cartilage and immunohistochemistry detection of extracellular matrix (ECM) or autophagy-related signal molecules. Meanwhile, human OA chondrocytes obtained from total knee replacement surgery patients with OA were cultured with the pretreatment of IL-1beta, followed with the treatment of PPARalpha agonist WY14643 and the detection of related signal molecules. RESULTS: PPARalpha deficiency aggravated cartilage damage with decreased LC3B level in combination with an increase in P62 level, accompanied with reduced p-Akt and p-ERK levels in PPARalpha-KO mouse model of experimental OA. On the contrary, PPARalpha activation by WY14643 promoted ECM synthesis in IL-1beta-treated human OA chondrocytes, accompanied with increased LC3B-II/I ratio and Beclin 1 level and decreased P62 and Bcl2 levels. Meanwhile, it was observed that activated ERK and Akt by PPARalpha activation contributed to the enhancement of autophagy and ECM synthesis in human OA chondrocytes. CONCLUSIONS: Impaired autophagy contributed to the aggravated deterioration of osteoarthritis articular cartilage by PPARalpha deficiency associated with the suppression of ERK and Akt, with an implication that triggering PPARalpha activation ought to be a potential promising therapeutic target for OA therapy. |
