Mendelian randomization analysis explores the causal relationship between cathepsins and osteoarthritis

Abstract

Osteoarthritis, a primary etiology of joint dysfunction, entails a multifaceted pathogenesis. Cathepsins, cysteine proteases localized within lysosomes, exert pivotal roles across diverse physiological and pathological contexts. Although observational inquiries suggest an interrelation between cathepsins and osteoarthritis, the etiological nexus remains elusive. Employing Mendelian randomization analysis, this investigation endeavors to elucidate this causal nexus. Univariate Mendelian randomization analysis reveals a plausible augmentation in osteoarthritis risk concomitant with a decline in cathepsin S levels. Conversely, reverse Mendelian randomization analysis posits that osteoarthritis might precipitate a reduction in cathepsin L2 levels. Multivariable analysis, encompassing 9 proteases as covariates, demonstrates a potential collaborative effect between elevated cathepsin F levels and diminished cathepsin S levels, thereby accentuating osteoarthritis risk. In summation, cathepsin S emerges as a prospective biomarker for osteoarthritis, conferring implications for diagnostic and therapeutic paradigms targeting this ailment.