title: Proliferation of rabbit chondrocyte and inhibition of IL-1β-induced apoptosis through MEK/ERK signaling by statins.
abstract: Chondrocyte plays a critical role in endochondral ossification and cartilage repair by maintaining the cartilaginous matrix. Statins have been widely used to lower the cholesterol level in patients with cardiovascular disorders. Previous research has demonstrated potential role of statins in chondrocyte proliferation. This study addresses the proliferation-regulatory effect of lovastatin in rabbit chondrocytes as well as the underlying signaling mechanisms, thereby exploring its potential application in chondrocyte-related disorders, such as cartilage damage and osteoarthritis. Rabbit chondrocytes were treated with lovastatin at multiple concentrations, and the proliferation rate was measured by CCK-8 test. The results showed significant increase in chondrocyte proliferation under lovastatin treatment. Using real-time quantitative PCR, it was observed that the expression levels of COL2A1, SOX-9, Caspase-3, and MMP-3 genes were significantly changed by lovastatin treatment. Western blotting analysis showed that the abundance of COL2A1, SOX-9, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, Caspase-3, and MMP-3 proteins was also significantly influenced by lovastatin treatment. Interleukine-1 beta (IL-1β) is involved in the progression of osteoarthritis (OA) by inducing articular cartilage and chondrocyte aging and senescence. In this study, we observed that lovastatin treatment inhibited IL-1β-induced chondrocyte apoptosis, while the combined treatment of lovastatin and U0126 evidently offset the apoptosis-inhibiting effect of lovastatin in chondrocyte proliferation. The expressional level and protein abundance of COL2A1, SOX-9, MEK1/2, p-MEK1/2, ERK1/2, p-ERK1/2, caspase-3, and MMP-3 genes showed significant alterations under the combined treatment. Together, our results suggested that lovastatin significantly promoted proliferation and inhibited the IL-1β-induced apoptosis in rabbit chondrocytes, which was mediated by the MEK/ERK signaling.
authors.affiliation: Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, XueYuan Road (West), LuCheng District, Wenzhou, ZheJiang Province, 325000, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, XueYuan Road (West), LuCheng District, Wenzhou, ZheJiang Province, 325000, China.
authors.forename: Deheng
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, XueYuan Road (West), LuCheng District, Wenzhou, ZheJiang Province, 325000, China. spinexu@163.com.
authors.forename: Huazi
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics, Zhejiang Provincial Key Laboratory of Orthopaedics, The Second Affiliated Hospital of Wenzhou Medical University, No. 109, XueYuan Road (West), LuCheng District, Wenzhou, ZheJiang Province, 325000, China. callmeroger@126.com.
authors.forename: Xiaolei
authors.identifier: http://orcid.org/0000-0003-3939-4345
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D008148:Lovastatin / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D011817:Rabbits
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D008148:Lovastatin; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Apoptosis; Chondrocyte; MEK/ERK signaling; Proliferation; Statin