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The loss of articular cartilage is the primary concern of OA, while subchondral bone plays a crucial role in the integrity of articular cartilage, providing mechanical support and nutrition supply and constantly adapting to the changing biomechanical environment in weight\u2010bearing joints. Osteocytes, abundant in subchondral bones, sense mechanical loading and control bone adaptive remodeling. Their bodies reside in lacunae and dendritic projections pass through tiny channels named canaliculi, together forming the lacunar\u2013canalicular system (LCS). The disorganization of osteocyte and LCS disrupts communication between osteocytes and other cells; it may contribute to OA initiation and or progression<jats:styled-content>.<\/jats:styled-content> In this review, insights into osteocyte as the master regulator of mechanosensation and mechanotransduction in bone remodeling by its mechanosensitive structures and dysregulation of osteocyte and LCS\u2010specific genes in OA are discussed. Finally, this review highlights emerging genetic and molecular targets, including Kindlin\u20102, PIEZO1, and Netrin\u20101, and discusses their potential in developing novel therapies. By integrating recent advances in mechanobiology, RNA\u2010based therapies, and nanotechnology, we propose a multi\u2010targeted approach to improve OA therapeutics. This review provides a comprehensive framework for understanding OA pathogenesis and identifies promising avenues for future research.<\/jats:p>","DOI":"10.1002\/jgm.70031","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T08:11:09Z","timestamp":1755245469000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Insights Into the Dysfunctional Communication Switches Targeting Osteocyte Mechanotransduction and Lacunar\u2013Canalicular Gene Network in Pathogenesis of Osteoarthritis"],"prefix":"10.1002","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4159-010X","authenticated-orcid":false,"given":"Shahneela","family":"Nusrat","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Faculty of Environment and Life, Beijing University of Technology  Beijing 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