| Longitudinal bone growth occurs at the growth plate by endochondral boneformation in which experienced chondrocytes proliferation, maturation, hypertrophyand finally apoptosis. The unique cellular architecture and kinetics of the growth platerequires multiple signaling pathways that act together to regulate the process of growthplate chondrogenesis. PTHrP（parathyroid hormone related protein）is secreted mainlyby periarticular chondrocytes, and it acts to induce chondrocyte proliferation andinhibit chondrocyte maturation and apoptosis in the growth plate. Ihh（Indianhedgehog）belongs to the vertebrate Hedgehog family of secreted morphogens and it ispredominantly secreted by prehypertrophic chondrocytes. Ihh can stimulate periarticular epiphyseal chondrocytes to synthesize PTHrP. PTHrP will in turndown-regulate Ihh expression, by acting on chondrocytes with PTH/PTHrP receptorsto keep the chondrocytes proliferating and to delay their conversion intoprehypertrophic and then hypertrophic chondrocytes. And so this forms a negativefeedback loop. Temporomandibular joint osteoarthritis（TMJOA）is a common andfrequently-occurring oral disease in clinic. However, the etiology and pathogenesis ofTMJOA remains obscure. The anomaly of Ihh/PTHrP signaling axis in condylarcartilages has been reported as the possible pathogenesis of OA. In this study, weestablish the rats model of experimentally created unilateral anterior crossbite for thefirst time, and investigate the effects of this occlusal disorder on the histology and theexpression of Ihh and PTHrP in mandibular condylar cartilage of Sprague-Dawley（SD）rats．Methods:Sixty6-week-old female SD rats weighing140-160g, were randomly and equallydivided into experimental group and control group. In experimental groups, theunilateral anterior crossbite metal prosthesis was cemented to the left incisors of themaxilla and mandible of SD rats, respectively. No treatment was applied to controlanimals, which were fed under the same environment till the end of the experiment.Animals were sacrificed at the end of2th,4th or8th week after the start of theexperiment．Hematoxylin-eosin（HE）staining were carried out for studying themorphological changes of the condylar cartilage．Immunohistochemica（lIHC）stainingand Real-time PCR analysis were performed to detect the levels of expression ofPTHrP, PTH1R, Ihh and Ptch in the condylar cartilages.Results:1. The results of HE staining: In the control group, the surface of condylarcartilage was smooth and continuous. Condylar cartilage was divided into fibrous layer,proliferative layer, mature and hypertrophic layers, with neat cell arrangement in each layer and clear boundaries. In2-week experimental subgroup, local chondrocytesdisarrangement was found, while small chondrocytes-free regions were seen in4-weekexperimental subgroup. However, in8-week experimental subgroup, OA-like changes,characterized by local homogeneous acidophilia staining region, chondrocytespyknosis, fibrous degradation, proliferating chondrocytes cluster and emptychondrocytes lacunae, were observed. In addition, compared to control subgroups, thenumber of chondrocytes increased in2-week experimental subgroup（P<0.01）, butdecreased in4,8-week experimental subgroup（both P<0.01）.2. The results of immunohistochemical staining: PTHrP and its receptor PTH1Rwere mainly expressed in the superficial zone of hypertrophic layer of condylarcartilage. In8-week experimental subgroup, the ratio of PTHrP-positive cell wasincreased than its age-matched control subgroup（P<0.01）, whereas the ratio ofPTH1R-positive cell was significantly decreased（P<0.01）. Ptch was mainly expressedin hypertrophic layer of condylar cartilage, and the ratio of Ptch-positive cell washigher in8-week experimental subgroup than the age-matched control group（P<0.01）.3. The results of Real-time PCR: In8-week experimental subgroup, the mRNAexpression levels of PTHrP and Ihh significantly increased compared with thecorresponding control（both P<0.01）, whereas PTH1R and Ptch mRNA levelsdecreased dramatically（both P<0.01）.Conclusion:1. TMJOA-like lesion in condylar cartilage of SD rat could be induced by theexperimentally created unilateral anterior crossbite prosthesis.2. Induced by the present abnormal occlusion, the expression of PTHrP, Ihh andPtch were up-regulated, while PRH1R was down-regulated. All these changes shouldbe a part of the constitution of the molecular pathomechanism of TMJOA-like lesioninduced by experimentally created unilateral anterior crossbite prosthesis. |
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