Investigating the role of immunohistochemical markers in driving ankylosis of the temporomandibular joint

Ankylosis is the process of bony or fibrous (sometimes mixed) adhesion of the joint components leading to restricted joint mobility and function. The temporomandibular joint (TMJ) is a bilateral diarthrodial joint that can undergo ankylotic changes either due to infections (primary etiology) or in cases of trauma and surgeries (secondary etiology). TMJ ankylosis is a condition mostly affecting young children and can often go undiagnosed for years before there is severe joint restriction manifesting as limited mouth opening and speech disturbances. Hence, an early diagnosis is crucial in providing patient with appropriate care and post-surgery rehabilitation.

Based on the therapeutic advantages, it becomes essential to investigate and study the complex pathoetiology of the healing processes in cases of TMJ ankylosis, especially the histological changes in the tissue microenvironment that governs these pathological changes. In the present study we investigated the TMJ ankylotic tissue samples that were collected during the primary surgery using various immuno-histochemical markers for tissue remodeling, inflammation, antimicrobial activity, and transcriptional regulation. The tissue samples were collected from a 6-year-old male child who underwent primary surgery following complaints of limited mouth opening. The boy underwent joint arthroplasty with rib autotransplantation i.e., 3 cm of fifth rib bone was harvested that was capped by 6 mm of costochondral cartilage. The material was a property of the Institute of Anatomy and Anthropology archive and its evaluation received permission of Riga Stradinš University Ethical committee 2-PEK-4/164/2022.

The collected tissue sample revealed that the child had developed bony ankylosis of the TMJ. In the tissue sample, we observed that the expression of matrix metalloproteinases (MMP-2,9,13) was either not there or was present in very low levels, indicating the absence of remodeling related changes in the bony tissue. However, moderate expression of MMP-8 was noted indicating its role in promoting anti-inflammatory tissue response. Furthermore, there was observed moderate to strong expression of TIMP metallopeptidase inhibitors-2 and -4. Such findings indicate an unbalanced MMP-2:TIMP-2 ratio (favoring TIMP-2) that is implicated in causing excessive accumulation of the extra-cellular matrix (ECM) in the joints and promotion of fibrotic changes due to localized tissue inflammation.

Low to moderate expression of growth factors like bFGF and FGFR-1 indicate towards slow healing processes in the bony tissue. Moreover, a moderate expression of IL-1 was noted, which indicates sustained background of inflammation. Moderate expression of β-defensin-2 was also found possibly showing ECM remodeling and collagen breakdown. Finally, low expression of RUNX-2 coupled with low expression of WNT-1 and -3a could indicate a slow and delayed bone regeneration process.

Our results showcase the complex myriad of pathways that could be involved in the progression of TMJA and post-surgery healing processes. Immunopathological investigations such as the present one could aid in improving diagnosis, treatment, and prognosis for patients affected with TMJ ankylosis.