The role of TGFβ1 and HTRA1 in the pathogenesis of TMJ osteoarthritis (922.8)

Abstract

The objective of this study is to understand the pathogenesis of osteoarthritis (OA) in the temporomandibular joint (TMJ) by testing for the presence of established biomarkers present in OA of the knee. Six wild‐type mice (M. musculus) and six mice heterozygous for the chondrodysplasia gene mutation (cho/+) were used in this study. The mice were euthanized at three months of age, and their TMJs were isolated, fixed, decalcified, embedded in paraffin, and sectioned at 6µ thickness. Fifteen sections of each mouse were stained with Safranin O and Fast Green to determine the extent of OA. Fifteen additional sections of each mouse were immunohistochemically stained for the presence of TGFß1 and HTRA1. Using the Modified Mankin and OARSI scoring systems, it was determined that OA is present in the TMJ of cho/+ mice but not in the wild type. Also, staining for TGFß1 and HTRA1 was positive in cho/+ TMJs and absent in the wild type. We have established that at three months of age, i.e., when early signs of OA histopathology are detectable, TGFß1 and HTRA1 are upregulated in the TMJ articular cartilage of cho/+ mice. We propose that TGFß1 is a biomarker for OA and can be used as an early diagnostic tool of TMJ OA. This finding is of clinical significance in light of the current practice to use TGFß1 as a therapeutic agent of TMJ OA. Despite the lack of type II collagen in TMJ articular cartilage relative to that of the knee joint, the presence of HTRA1 here suggests that the degenerative changes involve the same pathogenetic mechanism as in the knee joint. Grant Funding Source: NIH grant 1‐R15‐AR056861‐01A1