Research On The Function And Mechanism Of Condylar Cartilage Biomechanical Adaptability In The Temporomandibular Disorders

Objective Hypoxia inducible factor(HIF)-1α is critical for survival and growth of chondrocytes during cartilage development in healthy as well as osteoarthritic cartilage.We examined whether the HIF-1α and its target genes were involved in the mandibular condylar chondrocytes(MCCs)to hydrostatic pressure(HP)and Temporomandibular joint osteoarthritis(TMJ-OA),We also studied the effect of orthodontic force on TMJ.Methods Cell experimental study:MCCs were asptically dissected and cultured from the TMJ of 3-week-old SD rat in vitro.The MCCs of P3 were identified and were subjected to 200 KPa HP for 1,2,4,8 and 12 h.Expression of HIF-1α,VEGF and COL Ⅱ were examined by Western blot and quantitative real-time PCR.Animal experimental study:The right upper compartments of both TMJs of 48 male Sprague-Dawley rats were injected with 100μL Complete Freund’s Adjuvant to induce osteoarthrosis,the left sides as control group were injected with the same amount of normal sodium.The bilateral TMJs of 12 rats were harvested at 3,7,14 and 28 days.Histological changes in condylar cartilage were assessed by hematoxylin and eosin,toluidine blue,and safranin O staining.Expression of HIF-1α and VEGF were examined by Western blot and quantitative real-time PCR.Clinical study:By collecting clinical orthodontics case which sufferred from TMJ symptoms before and after orthodontics treatment,analysised medical records,photos about before and after orthodontic treatment,imageing data and so on.Results1.The mRNA and protein expression levels of HIF-1α,VEGF and COLⅡwere significantly increased in a time-dependent manner,reached maximal levels at 4 h of 200 KPa HP stimulation(P<0.05).2.The histological analysis showed marked cartilage degeneration in adjuvant-induced OA groups,including reduced cartilage cellular density,thinner and degraded cartilage,and decreased proteoglycan content in the extracellular matrix.3.The mRNA and protein expression levels of HIF-1α,VEGF were significantly increased in a time-dependent manner,reached maximal levels at 14 d in the OA groups compared with matched control groups(p<0.001).4.A variety of orthodontic forces may cause TMJ adaptive morphological changes and alterations.Once the orthodontic force exceeds the body’s regulation range,that can lead to pathological changes in the TMJ,even cause TMD or TMJ-OA.With the extension of time,TMJ,nerves,masticatory muscles and occlusal relationships reach a new balance,TMD symptoms will improve or disappear.Conclusion The MCCs has a certain ability to pressure micro-changes in circumstances.HP induced HIF-1α and its target gene expression in MCCs,and HIF-1α-VEGF signaling may be correlated with pathological changes of condylar cartilage in adjuvant-induced TMJ-OA.