AB0103 A NOVEL PROTECTIVE ROLE OF GPNMB/OSTEOACTIVIN IN POST-TRAUMATIC OSTEOARTHRITIS
Authors: Asaad Al Adlaan, Nazar Hussein, Fatima Jaber, Fayez Safadi
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Osteoarthritis (OA) is a chronic joint disease causes irreversible damage to the articular cartilage resulting in loss of joint function and subchondral bone remodeling. There is no cure for OA and currently the available treatment like pain management, and joint replacement surgery is used to treat this disease. GPNMB/Osteoactivin is a type-I transmembrane protein plays a vital role in osteogenesis and bone remodeling, <h3>Objectives:</h3> Howver, the function of GPNMB/Osteoactivin in chondrogenesis and cartilage repair is unknown. Hence, in this study, we examined the role of GPNMB/Osteoactivin using post-traumatic osteoarthritis model and ex vivo chondrocytes cell culture and assessing the effects of GPNMB/Osteoactivin as anti-inflammatory factor in chondrocytes. <h3>Methods:</h3> We first examined the expression GPNMB/Osteoactivin in noramal cartilage. Next, we assessed the effects of recombinant GPNMB/Osteoactivin on mouse primary chondrocytes profeliation/viabiltiy and extracellular matrix marekrs. <h3>Results:</h3> We founad that GPNMB/Osteoactivin treatment did not have any effect on cell prolfieration/viability, howwever, there was an increased in Colllagen Type II and aggrecan expression in a dose- and time-dependent manner. These data sugges that GPNMB/Osteoactivin palys a role in cartilage maintainance. Next we determined whether GPNMB/Osteoactivin contributes to the OA disease progression. Human osteoarthritic damaged and undamaged cartilage harvested following knee replacement were used to examine GPNMB/Osteoactivin exmression and founad that GPNMB/Osteoactivin mRNA was 6-7-fold increased in damaged compared to undamaged cartilage. Similar results were obtained from mouse primary chondrocytes treated with IL1-b and showed a significant increase (4-fold) in GPNMB/Osteoactivin mRNA compared to untreated control. Next, we evalauted the effects of GPNMB/Osteoactivin deficiency on the OA progression usign the DMM model. GPNMB/Osteoactivin muntat (DBA/2J) mice showed significant increased in OARSI scores compared to WT mice. <h3>Conclusion:</h3> Taken together, these data are the first to report a role for GPNMB/Osteoactivin in cartilage maintanance and protection again the prgoression of OA. <h3>References</h3> [1] The surgical destabilization of the medial meniscus (DMM) model of osteoarthritis in the 129/SvEv mouse. Methods in Molecular Biology: Osteoporosis and Osteoarthritis. Loeser RF, Goldring SR, Scanzello CR, Goldring MB. Osteoarthritis: A disease of the joint as an organ. Arthritis and Rheumatism. 2012. pp. 1697–1707. [2] Zhou, L., Zhuo, H., Ouyang, H., Liu, Y., Yuan, F., Sun, L.,. .. &amp; Liu, H. (2017). Glycoprotein non-metastatic melanoma protein b (Gpnmb) is highly expressed in macrophages of acute injured kidney and promotes M2 macrophages polarization. Cellular immunology, 316, 53-60. [3] Ripoll, V.M., et al., Gpnmb is induced in macrophages by IFN-gamma and lipopolysaccharide and acts as a feedback regulator of proinflammatory responses. J Immunol, 2007. 178(10): p. 655766. [4] Karlsson C, Dehne T, Lindahl A, Brittberg M, Pruss A, Sittinger M, Ringe J. Genome-wide expression profiling reveals new candidate genes associated with osteoarthritis. Osteoarthritis and Cartilage. 2010Apr1;18(4):581-92. <h3>Acknowledgement:</h3> This research was funded in part by the Cook Research Fund, Summa Heatlh System and Ohio Department of Education <h3>Disclosure of Interests:</h3> None declared