Activation of TGF-β Smad Signaling Promotes Temporomandibular Joint Injury Repair in Aged Rats

Background: Temporomandibular joint (TMJ) disorders are common in adults, leading to cartilage degradation and joint dysfunction. Transforming growth factor-beta (TGF-β) has been found to increase extracellular matrix synthesis and suppress inflammation in osteoarthritis; however, its specific role in TMJ disorders remains uninvestigated. Therefore, this study aims to explore the involvement of TGF-β in TMJ injury repair, particularly examining its effects in aged rats. Methods: The Sprague-Dawley rats were assigned to young (n = 10) and aged (n = 30) groups, with TMJ injury induced using type II collagenase. TGF-β was injected to activate the TGF-β/Smad signaling pathway, while SB431542 was used as an inhibitor of the pathway. Histological analysis (hematoxylin and eosin [H&E] staining and Safranin O/Fast Green staining) was used to examine cartilage repair, and Western blot analysis was employed to determine changes in TGF-β/Smad pathway and cartilage matrix-related proteins. Furthermore, head withdrawal threshold (HWT) and feeding behavior were evaluated to determine the impact of TGF-β treatment on pain sensitivity and feeding behavior. Results: TGF-β treatment significantly improved cartilage repair in aged rats following TMJ injury. Histological analysis revealed increased cartilage thickness, improved cell arrangement, and reduced proteoglycan depletion in the TGF-β group. Western blot analysis demonstrated substantially elevated phosphorylated-Smad2/Smad2 (p-Smad2/Smad2) and p-Smad3/Smad3 ratios in the TGF-β group (<i>p</i> < 0.01). Furthermore, TGF-β treatment upregulated the expression of Aggrecan and Collagen II, while downregulating the levels of matrix-degrading enzymes matrix metalloproteinase-13 (MMP-13), matrix metalloproteinase-3 (MMP-3), and A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) (<i>p</i> < 0.01). Additionally, the TGF-β group had significantly reduced pain sensitivity and improved feeding behavior compared to the injury group (<i>p</i> < 0.05). In contrast, SB431542 treatment aggravated cartilage degradation, increased proteoglycan loss, elevated matrix-degrading enzymes, and worsened pain sensitivity (<i>p</i> < 0.05). Conclusion: TGF-β activation promotes cartilage repair in aged rats with TMJ injury by enhancing extracellular matrix synthesis and reducing degradation, offering a novel approach for treating age-related TMJ disorders.