Nate Baruch

Introduction: Osteoarthritis (OA) is a degenerative joint disease in which progression is marked by thinning and destruction of articular cartilage, and irreversible loss of chondrocytes[1]. Damage may occur by physiological wear and tear, or otherwise be due to pathological inflammatory processes[2]. Due to the irreversible cell loss and poor understanding of the molecular pathogenesis of OA, surgical joint replacement remains the only effective means of stopping disease progression1-2. However, with further research helping to unveil the molecular mechanisms involved, new therapeutic targets may emerge. Increasing evidence supports 15-LO-1 playing a crucial role in the pathogenesis of OA making it a potential therapeutic target3. Methods: Primary research articles conducted between 2013 and 2018 with a focus on the role of Lipoxygenase enzymes were analyzed. These studies utilized both rat and human models to determine the relationship between 15-LO-1 and various pathological processes, and more specifically 15-LO-1 in OA pathogenesis. Results: 15-LO-1 is specifically upregulated in weight bearing portions of cartilage3. 15-LO-1 has also been shown to increase chondrocyte production of reactive oxygen species (ROS), which then cause cell death and extracellular matrix (ECM) degradation4,5. Furthermore, silencing 15-LO-1 expression alleviates biomechanical load-induced ROS production3. 15-LO-1 is additionally involved in chondrocyte apoptosis, a key process in OA, and its silencing resulted in significantly reduced apoptosis induction in chondrocytes3,6. Conclusions: 15-LO-1 is implicated in the pathogenesis of OA though its exact role and ability to be manipulated in vivo remain uncertain. Further research must be done to elucidate the exact role of 15-LO-1 and other molecules in OA, and determine their viability as therapeutic targets.

1. Xia B, Chen D, Zhang J, Hu S, Jin H, Tong P. Osteoarthritis Pathogenesis: A Review of Molecular Mechanisms. Calcified tissue international. 2014;95(6):495-505. doi:10.1007/s00223-014-9917-9.
2. Houard X, Goldring MB, Berenbaum F. Homeostatic Mechanisms in Articular Cartilage and Role of Inflammation in Osteoarthritis. Current rheumatology reports. 2013;15(11):375. doi:10.1007/s11926-013-0375-6.
3. Chen K, Yan Y, Li C, et al. Increased 15-lipoxygenase-1 expression in chondrocytes contributes to the pathogenesis of osteoarthritis. Cell Death & Disease. 2017;8(10):e3109-. doi:10.1038/cddis.2017.511.
4. Li, Qian et al. “Key Role of ROS in the Process of 15-Lipoxygenase/15-Hydroxyeicosatetraenoiccid-Induced Pulmonary Vascular Remodeling in Hypoxia Pulmonary Hypertension.” Ed. Tim Lahm. PLoS ONE 11.2 (2016): e0149164. PMC.
5. Buckwalter, Joseph A. et al. “The Roles of Mechanical Stresses in the Pathogenesis of Osteoarthritis: Implications for Treatment of Joint Injuries.”Cartilage 4.4 (2013): 286–294. PMC. Web. 23 Apr. 2018.
6. Wu GJ, Chen TG, Chang HC, Chiu WT, Chang CC, Chen RM. Nitric oxide from both exogenous and endogenous sources activates mitochondria-dependent events and induces insults to human chondrocytes. J Cell Biochem 2007; 101: 1520–1531.