The mandibular condyles represent important growth sites within the facial skeleton. Condylar growth is not a pacemaker of mandibular development, but it provides regional adaptive growth that is of considerable clinical significance, as the condyle’s upward and backward growth movement regulates the anteriorly and inferiorly directed displacement of the mandible as a whole. Orthopedic problems of the temporomandibular joint (TMJ), such as displacement of the TMJ disk, are common in the adolescent population. Clinical studies of mandibular asymmetry and mandibular retrognathia in adults as well as in children and adolescents, have reported an association with coexisting non-reducing displacement of the TMJ disk without identifying the cause and effect. Through experimental studies causality has been established, and unilateral affliction during growth has been shown to retard ipsilateral mandibular development with facial asymmetry as the sequel. It was hypothesized that bilateral non-reducing TMJ disk displacement during growth would impair mandibular development bilaterally, resulting in mandibular retrognathia. TMJ disk displacement has repeatedly been demonstrated to induce histological reactions of the condylar cartilage. An additional assumption was therefore that a non-deranged TMJ disk function is crucial for the maintenance of the growing condyle’s biophysical environment, and that a connection ought to exist between the amount of condylar cartilage changes caused by TMJ disk displacement and the amount of subsequent adverse mandibular growth. It was also hypothesized that non-reducing displacement of the TMJ disk in growing individuals would result in qualitative and quantitative changes of the condylar subchondral bone. An improved experimental cephalometric method was developed in order to optimize the reliability of longitudinal radiographic evaluation of fast growing small animals. Bilateral non-reducing TMJ disk displacement was surgically created in ten growing New Zealand White rabbits, with ten additional rabbits serving as a sham operated control group. The amount and direction of craniofacial growth was followed over time in serial cephalograms, aided by tantalum implants in the jaws. The study period was chosen to correspond to childhood and adolescence in man. The assessed growth of each side of the mandible was correlated to the histological feature of ipsilateral condylar cartilage at the end of the growth period. The amount and composition of subchondral bone from three regions of interest in the condyle, and the expression of local growth factors in the adjacent condylar cartilage was evaluated. The results verified that bilateral non-reducing TMJ disk displacement retarded mandibular growth bilaterally; the extent corresponding to mandibular retrognathia in man. Displacement of the TMJ disk during the growth period induced condylar cartilage adaptive reactions that were associated with both an adverse amount and direction of mandibular growth, manifesting in a retrognathic mandibular growth pattern. Growth impairment fluctuated over time, with the most striking retardation occurring during periods of increased general growth, implying a local growth reduction explicitly counteracting general hormonal growth acceleration. A significant decrease of the total amount of subchondral bone, in spite of a general increase of new bone formation in the experimental condyles, pointed to a reparative compensation for an extensive resorption of subchondral bone due to displacement of the TMJ disk, but not to the extent that normal growth would be maintained. These results constitute an explanation for the adverse mandibular development following non-reducing TMJ disk displacement in growing individuals. This project has shown that non-reducing displacement of the TMJ disk during growth has significant consequences on facial development. The findings strongly advocate early and accurate diagnosis and treatment of TMJ disk displacement in the adolescent population, thereby presumably reducing the need for future orthodontic and surgical craniofacial corrective therapy. The results furthermore enhance the need for full appraisal of TMJ disk function in the adolescent population during orthodontic functional therapy, as the condylar cartilage and subchondral bone reactions to a concomitantly displaced non-reducing TMJ disk must be expected to interfere with the intended growth stimulating treatment. The findings of intact articular layers in spite of gross histological and morphological soft and hard tissue changes as a sequel to TMJ disk displacement in growing individuals, implicate a clinical risk of false positive radiographic diagnosis of degenerative changes of the TMJ in children and adolescents.

Abstract The temporomandibular joint (TMJ) is a synovial joint which attaches the mandible to the skull. The head of the mandibular condyle is covered by condylar cartilage, which functions as both growth and articular cartilage. Masticatory forces are transmitted to the condylar cartilage, and the consistency of a person’s diet partly defines the loading force. Condylar cartilage acts as a load-absorbing structure together with the articular disc. Temporomandibular disorders (TMDs) are a wide group of pathological conditions involving pain and dysfunction in the masticatory system. Females comprise the majority of patients, having more symptoms and clinical signs than men. Because of this gender distribution, it has been suggested that the female sex hormone estrogen has an influence on the pathogenesis of TMJ osteoarthrosis. However, little is known about how estrogen affects condylar cartilage. The effect of estrogen deficiency and altered dietary loading on condylar cartilage was studied with female rats, which were distributed to four groups depending on ovariectomy and diet consistency, and further to two distinct age groups. Expression of type II and X collagens, adiponectin, ERα, MMP-3, MMP-8, TRAP, and cathepsin K was investigated. Markers of apoptosis and proliferation of cartilage cells were investigated. A lack of estrogen increased and a soft diet decreased the thickness of condylar cartilage. Expression of proliferating cell nuclear antigen (PCNA, proliferation marker) was higher in ovariectomized rats fed a normal diet when compared with control rats. The area of type II and X collagens in condylar cartilage was larger when estrogen was not present and smaller when the diet consistency was soft. Expression of MMP-3 was higher in ovariectomized rats than in control rats. Ovariectomized rats fed a soft diet had higher expression of MMP-8 than ovariectomized rats fed a normal diet. However, control rats fed a soft diet had lower proportional expression of MMP-8 than normal diet controls. The proportional amount of cartilage cells stained against adiponectin was higher in rats fed a soft diet when compared with rats fed a normal diet. The proportional amount of cartilage cells expressing ERα was higher in ovariectomized rats than in control rats. Osteoclast markers cathepsin K and TRAP showed that ovariectomized rats had fewer osteoclasts than control rats had. The average size of osteoclasts was smaller in ovariectomized rats when compared with control rats. The results of this study show that estrogen and altered dietary loading have an effect on condylar cartilage. Further studies are needed to evaluate the significance of these changes, and especially their association with TMJ disorders. / Tiivistelmä Leukanivel on synoviaalinivel, joka liittää mandibulan eli alaleuan kalloon. Alaleuan nivellisäkkeen eli kondyylin päässä oleva rustokerros toimii sekä kasvu- että nivelrustona. Purentavoimat välittyvät kondyylirustoon, ja kuormituksen määrä on riippuvainen ruoan kovuusasteesta. Kondyylirusto toimii kuormituksen vastaanottajana yhdessä nivelvälilevyn kanssa. Purentaelimistön toimintahäiriöihin (TMD) kuuluu laaja joukko patologisia tiloja, joihin liittyy kipua ja dysfunktiota purentaelimistössä. Potilaista suurin osa on naisia, ja heillä on oireita sekä sairauden kliinisiä tunnusmerkkejä enemmän kuin miehillä. Sukupuolijakaumasta johtuen on arveltu, että naissukupuolihormoni estrogeenilla voisi olla vaikutusta leukanivelartroosin patogeneesiin. Tällä hetkellä tietoa on hyvin vähän siitä, miten estrogeeni vaikuttaa leukanivelrustoon. Estrogeenin puutoksen ja muunnellun purentarasituksen vaikutusta leukanivelrustoon tutkittiin naarasrotilla, jotka jaettiin neljään eri ryhmään munasarjojen poiston ja dieetin kovuusasteen mukaan sekä lisäksi kahteen eri ikäryhmään. Tyypin II ja X kollageenin, adiponektiinin, estrogeenireseptori α:n, MMP-3:n, MMP-8:n, TRAP:n ja katepsiini K:n ekspressio tutkittiin. Rustosoluista tutkittiin apoptoosin ja proliferaation merkkiaineet. Estrogeenin puute lisäsi ja pehmeä dieetti pienensi kondyyliruston paksuutta. PCNA:n (proliferating cell nuclear antigen) ekspressio oli suurempi normaalilla dieetillä olleilla ovariapoistetuilla rotilla kuin kontrollirotilla. Tyypin II ja X kollageenien osuus oli suurempi ovariapoistettujen rottien kondyylirustossa kuin pehmeällä dieetillä olleilla. MMP-3:n ekspressio oli korkeampi ovariapoistetuilla rotilla kuin kontrolleilla. Ovariapoistetuilla rotilla, jotka olivat pehmeällä dieetillä, oli suurempi MMP-8:n ekspressio kuin normaalilla dieetillä olleilla ovariapoistetuilla rotilla. Kuitenkin MMP-8:n ekspressio oli pienempi pehmeällä dieetillä olleilla kontrollirotilla kuin normaalilla dieetillä olleilla. Adiponektiinin tunnistavalle vasta-aineelle positiivisten solujen suhteellinen lukumäärä oli suurempi pehmeällä dieetillä olleilla rotilla kuin normaalilla dieetillä olleilla. Estrogeenireseptori α:a ekspressoivien solujen suhteellinen lukumäärä oli suurempi ovariapoistetuilla rotilla kuin kontrolleilla. Osteoklastien merkkiaineet katepsiini K ja TRAP osoittivat, että ovariapoistetuilla rotilla oli vähemmän osteoklasteja kuin kontrollirotilla. Osteoklastien keskimääräinen koko oli pienempi ovariapoistetuilla rotilla kuin kontrolleilla. Tutkimuksen tulokset osoittavat, että estrogeeni ja muunneltu purentarasitus vaikuttavat leukanivelrustoon. Lisätutkimuksia tarvitaan, jotta voidaan arvioida näiden muutosten merkitsevyys ja erityisesti niiden yhteys leukanivelen toimintahäiriöihin.