IADR Abstract Archives
Exploring a Patient-Centered Approach to Temporomandibular Disorders at the NIH
Objectives: Temporomandibular disorders (TMD) present a significant healthcare challenge in the US due to their complex and elusive origins. Despite distinct anatomical structures, the temporomandibular joint (TMJ) and synovial facet joint exhibit substantial similarities in receptor-mediated pathological processes, including integrin and TGF-β signaling abnormalities during degenerative processes. To address the unmet needs of TMD patients, we established a patient-centered strategy that involves a multidisciplinary consortium dedicated to understanding TMD while identifying appropriate patient cohorts. The aim of this study is to compare the TMD onset in healthy and syndromic patients at risk for TMD.
Methods: Using an IRB-approved protocol (#16-D-0040), we evaluated a unique patient cohort with Loeys Dietz syndrome (LDS) who have altered TGF-β signaling pathways to identify early-onset TMJ abnormalities. We compared this cohort to healthy volunteers. Our methods include clinical phenotyping, 3D image morphometrics and patient data-driven models using a chair-side TMJ structure-function-pain assessment. Concurrently, we employed an LDS mouse model and patient-derived induced pluripotent stem cells (iPSCs).
Results: In our evaluation of LDS subjects, we observed early-onset TMJ osteoarthritic changes compared to healthy volunteers. Morphologically, individuals with LDS were distinct from the healthy volunteers and demonstrated consistent retrognathia, cranial base abnormalities and TMD symptoms at a younger age. This pattern was mirrored in mice carrying the TGFBR2G357W/+ mutation, recapitulating LDS phenotypes. We successfully established iPSCs from both healthy and individuals with LDS for our ongoing experimental work to unravel how alterations in the TGF-β signaling pathway contribute to the development of degenerative TMJ syndromes.
Conclusions: Altered TGF-β signaling plays a key role in the early onset of TMJ abnormalities. Patient-derived iPSC-based disease modeling can provide valuable insights that may contribute to identifying effective therapeutic approaches. Our consortium emphasizes sustaining multidisciplinary research and enhancing patient-centered assessment and risk stratification for TMD.
Methods: Using an IRB-approved protocol (#16-D-0040), we evaluated a unique patient cohort with Loeys Dietz syndrome (LDS) who have altered TGF-β signaling pathways to identify early-onset TMJ abnormalities. We compared this cohort to healthy volunteers. Our methods include clinical phenotyping, 3D image morphometrics and patient data-driven models using a chair-side TMJ structure-function-pain assessment. Concurrently, we employed an LDS mouse model and patient-derived induced pluripotent stem cells (iPSCs).
Results: In our evaluation of LDS subjects, we observed early-onset TMJ osteoarthritic changes compared to healthy volunteers. Morphologically, individuals with LDS were distinct from the healthy volunteers and demonstrated consistent retrognathia, cranial base abnormalities and TMD symptoms at a younger age. This pattern was mirrored in mice carrying the TGFBR2G357W/+ mutation, recapitulating LDS phenotypes. We successfully established iPSCs from both healthy and individuals with LDS for our ongoing experimental work to unravel how alterations in the TGF-β signaling pathway contribute to the development of degenerative TMJ syndromes.
Conclusions: Altered TGF-β signaling plays a key role in the early onset of TMJ abnormalities. Patient-derived iPSC-based disease modeling can provide valuable insights that may contribute to identifying effective therapeutic approaches. Our consortium emphasizes sustaining multidisciplinary research and enhancing patient-centered assessment and risk stratification for TMD.