Sex Specific Determinants in Osteoarthritis: A Systematic Review of Preclinical Studies

Osteoarthritis (OA) is a highly prevalent joint disease that primarily affects about 10% of the world's population over 60 years old. The purpose of this study is to systematically review the preclinical studies regarding sex differences in OA, with particular attention to the molecular aspect and gene expression, but also to the histopathological aspects. Three databases (PubMed, Scopus, and Web of Knowledge) were screened for eligible studies. In vitro and in vivo papers written in English, published in the last 11 years (2009-2020) were eligible. Participants were preclinical studies, including cell cultures and animal models of OA, evaluating sex differences. Independent extraction of articles and quality assessments were performed by two authors using predefined data fields and specific tools (Animals in Research Reporting In Vivo Experiments (ARRIVE) guideline and Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool). Twenty-three studies were included in the review: 4 in vitro studies, 18 in vivo studies, and 1 both in vitro and in vivo study. From in vitro works, sex differences were found in the gene expression of inflammatory molecules, hormonal receptors, and in responsiveness to hormonal stimulation. In vivo research showed a great heterogeneity of animal models mainly focused on the histopathological aspects rather than on the analysis of sex-related molecular mechanisms. This review highlights that many gaps in knowledge still exist; improvementsin the selection and reporting of animal models, the use of advanced in vitro models, and multiomics analyses might contribute to developing a personalized gender-based medicine.