Urotensin-II Prevents Cartilage Degeneration in a Monosodium Iodoacetate-Induced Rat Model of Osteoarthritis

Abstract

Osteoarthritis (OA) is a common degenerative articular disorder caused by traumatic or spontaneous factors such as genetics, obesity, and advanced age. Comprehending the pathogenic mechanism of OA ensures the development of novel disease-modifying therapeutics rather than conventional palliative drugs with undesired side effects. Urotensin-II (UII) is a multifunctional short cyclic peptide implicated in several disorders. We aimed to analyze the effects of intraarticular UII treatment in a monosodium iodoacetate (MIA)-induced OA rat model. We divided animals into six groups to test three different concentrations of UII with histopathological and immunohistochemical analyses of bone morphogenetic protein-2 (BMP-2), nuclear factor kappa B subunit 1 (NF-kappa B), and intrinsic UII expression. We analyzed serum levels of cartilage related and inflammatory markers post-OA. We observed a noticeable amelioration of the MIA-induced knee damage in UII-treated animals after gross morphology examination. Mankin scoring after histopathological stainings revealed a partial prevention of articular tissue damage in UII-treated animals. We found a significant reduction in BMP-2 and NF-kappa B while an increase in intrinsic UII expressions upon exogenous UII injection after immunohistochemical analyses. The Mankin scores were significantly correlated with BMP-2, NF-kappa B, and intrinsic UII levels. There was no significant alteration in serum markers after UII treatment. We are the first group showing the protective effect of UII on the destructed knee joints of osteoarthritic rats by downregulating the BMP-2 and NF-kappa B and upregulating intrinsic UII expressions. To uncover the mechanistic role of UII during OA, further experiments are warranted. [GRAPHICS] .