Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

Abstract

As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.

Mechanistic insights into the role of the chemokine CCL2/CCR2 axis in dorsal root ganglia to peripheral inflammation and pain hypersensitivity

“…Although RA and OA are two very different conditions, they share some common symptoms, such as joint pain, stiffness, and swelling. Furthermore, while inflammation is usually associated with RA, there is now growing evidence indicating that OA is also tied to inflammation [ 26 , 27 ]. Consequently, ongoing joint inflammation is thought to play a key role in peripheral and central pain sensitization in inflammatory arthritis [ 28 ].…”

Experimental Therapeutics for the Treatment of Osteoarthritis

“…Diverse pathogenetic factors in OA have been identified including its initiation by insufficient cartilage healing after injury representing posttraumatic OA (PTOA), loss of function of cartilage during aging, 11 genetic predispositions (eg, less stable cartilage ECM through mutations in ECM genes or less effective protective mediators due to mutations in their genes) or joint overload (by misalignment of leg axis or adipositas/obesity as well as meniscus damage or loss). 12 , 13 The contribution of metabolic dysbalances (metabolic syndrome, diabetes mellitus) to OA has been underlined in the last years. 14 , 15 Joint pain, stiffness and swelling are typical clinical features of OA.…”

“…There are no approved effective disease-modifying OA drugs (DMOADs) available for OA treatment. 12 Only symptomatical treatment of OA can be performed. Hence, analgesics and non-steroidal anti-inflammatory drugs (NSAIDs) addressing pain and inflammation are the therapeutic options for OA 45 , 46 with adverse effects in long-term use.…”

Osteoarthritis, osteoarthrosis and osteoarthropathy: What is the difference?

“…Zapravo bi se moglo reći da degeneracija jeste starenje. Starenje, koje karakteriše progresivni gubitak funkcije tkiva i organa tokom vremena, predstavlja najveći pojedinačni faktor rizika za osteoartrozu [12].…”