Involvement of TGF-β1 in the Initial Phase of TMJ Osteoarthritis

Objectives: The objective of this study was to elucidate OA progression in an animal model of Stickler syndrome, assess the expression of identified inflammatory markers associated with OA, viz., TGFß1 and HtrA1, and provide mechanistic insights based on their levels of expression.
Methods: The study involved mice containing an autosomal semidominant disproportionate micromelia (Dmm/+) mutation in the C-propeptide coding region of the Col2a1 gene. Specifically, eight control (+/+) and eight heterozygous (Dmm/+) mice were evaluated. The mice were euthanized at two and six months of age, and their TMJs were isolated, fixed, decalcified, embedded in paraffin, and sectioned at 6µ thickness. To determine OA status, tissues were stained with Safranin O to identify proteoglycans and counterstained with Fast Green. The extent of staining and onset of OA were quantified using Modified Mankin and OARSI scoring systems. Selected sections of each genotype were also immunohistochemically stained for the presence of TGFß1 and HtrA1, two inflammatory mediators that have been identified to play a role in OA progression.
Results: The results revealed Mankin and OARSI scores consistent with OA-like changes. These changes were detectable as early as two months in Dmm/+ mice when compared with normal joint biology observed in control animals. Compared to basal expression in control TMJs, staining for TGFß1 and HtrA1 demonstrated augmented expression in Dmm/+ mice as early as two months of age, with overexpression persisting in six-month-old mutant mice.
Conclusions: Two months of age generally coincides with the initial detection of OA histopathology. Our study demonstrated that TGFß1 and HtrA1 are overexpressed in TMJ articular cartilage of two-month–old Dmm/+ mice when compared with age-matched controls. Early TGFb1 and HtrA1 levels suggest that both inflammatory mediators are involved in the earliest stages of TMJ OA. Further studies could shed light on HtrA1 and TGFB1 use as possible targets for therapeutic intervention.