LOXL2: Its Expression and Role in TMJ Disease

Statement of Problem: Temporomandibular joint (TMJ) disorders include a group of complex and poorly understood conditions that are characterized by orofacial pain, joint sounds, and restricted joint movement that leads to anatomical changes. Osteoarthritis (OA) is a degenerative disease (DJD) with changes in joints including defective extracellular matrix (ECM) remodeling, reduced collagen-networking and chondrocyte apoptosis. Lysyl oxidase (LOX) family members (LOX, LOXL1-4) are copper-dependent amine oxidases and, in general, have roles in ECM remodeling and collagen cross-linking and have very recently been linked to knee-OA. The purpose of this study is to determine  the expression of LOXL2  in human TMJ tissues affected with DJD.

Materials and Methods: We obtained control, mild and late clinical stage TMJ-OA subjects from the subjects undergoing TMJ surgery. Exclusion criteria included a history of any systemic inflammatory condition or cancer. The samples were divided on the basis of diagnostic pathological finding as no OA, mild- and severe–OA. The slides were scored for the presence of OA based on a modified Mankin system,  and a semi-quantitative histological scoring system was used to investigate degenerative changes in the mandibular condylar cartilage. All slides were immunostained with anti-LOXL2 antibodies. The effect of LOXL2 overexpression in OA chondrocytes was evaluated by global gene array analysis, gene set enrichment analysis (GESA) and on IL-1β- and TNF-α- induced phenotypic changes

Conclusions: The results of this pilot study show that LOXL2 is expressed in clinically progressive OA, has a role in the pathophysiology and could promote anabolic and regenerative responses in OA. This is the first study to identify a role for LOXL2 in TMJ OA. The increase in LOXL2 expression is similar in time and magnitude to that of BMP2, suggesting that it could be a compensatory anabolic response due to degenerative changes in OA. LOXL2 has a specific role as a structure-modifying and anabolic agent in cartilage regeneration during OA and its discovery could hold promise for future biologic treatment of OA.

References:1. Iftikhar M, Hurtado P, Bais MV, Wigner N, Stephens DN, Gerstenfeld LC, Trackman PC. Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically required for differentiation. J Biol Chem. 2011;286(2):909-18. Epub 2010/11/13. doi: M110.155622 [pii] 10.1074/jbc.M110.155622. PubMed PMID: 21071451; PubMed Central PMCID: PMC3020776

2. Haskin CL, Milam SB, Cameron IL. Pathogenesis of degenerative joint disease in the human temporomandibular joint. Crit Rev Oral Biol Med 1995; 6: 248-277