Project description:Mandibular condylar cartilage (MCC) has many distinctive features reviewed in the literature, hence it would be expected that the genetic regulation of the biological process in the MCC to be different from those of other articular hyaline cartilages and epiphyseal growth cartilages. In addition, The MCC is a multi-zonal fibrocartilage containing different types of cells, which are well characterized histomorphologically, but the factors governing their morphological transition across the zones are not fully understood. Therefore, we can speculate that unique genetic profiles in vivo might exist within the four zones of MCC. We used microarrays to obtain new insights into the MCC cells by performing a comprehensive zone-specificgene expression profile analysis for each zone of the MCC isolated from 5-week-old rats using LCM technology and compare it to femoral condylar cartilage (FCC) profiles.
Project description:An organoid culture system can better recapitulate the cellular structure, function, and interaction between cells and the extracellular matrix (ECM) than the traditional two-dimensional (2D) culture system. We here constructed a condylar cartilage organoid and utilized it to explore the regulatory role of primary cilia at the organoid level. RNA sequencing unveiled the differences of transcriptomics between the condylar cartilage organoid and 2D culture chondrocytes.
Project description:Although our data is providing the evidence that Ihh regulates nasal and mandibular cartilage development to establish facial and masticatory system, the cartilage gene network conducted by Ihh signaling has not been broadly investigated. To establish such gene expression profile, we selected mandibular condylar cartilage to examine differentiating cartilage tissue. The cartilage histologically indicates simple endochondral ossification and mutant sections positive to Tomato staining presented decreased and disrupted cartilage.
Project description:Internal derangement (ID) in the temporomandibular joint (TMJ) compromises a group of clinical problems, and holds a relative high prevalence in populations. However, the temporal change in gene expression of condylar cartilage during continous ID remains unclear. The aim of current study is investigating the differential expressed gene pattern in condylar cartilage of rabbits with ID from 1 to 8 weeks. Immunohistochemical results indicated that abnormal collagen fiber arrangements, fragmentation of fibrils, inflammatory cells infiltration were detected from 1 week to 4 week in joint disc specimens, while newly formed vessels, mucoid degeneration, meniscal tears, osteoclasts and osteoblasts were observed later. The microarray analysis showed 6478 genes have more than two-fold changes among all the tested transcripts. The inflammation gene group including ACE and IL1βincreased rapidly in the early stage while decrease later. On the contrary, the bone construction related genes showed a low level at first and increased at later period in the ID progression. Besides, the current study found some genes such as HLA2G, which had never been reported, might be relevant with ID. Our findings might provide useful insights into the pathological mechanism of ID in TMJ.
Project description:Background Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. Materials and Methods To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. Results Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclast in the subchondal bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. Conclusions Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.
Project description:BACKGROUND: Estrogens play an important role in modulating the morphology and function of temporomandibular joints (TMJs), which is suggested to act via estrogen receptors (ERs). The present study was to investigate the expression of aggrecan, collagen type II (Col II), Col X, aromatase, ER? and ER? in degenerative changes of mandibular condylar cartilage. METHODS: Forty male and 40 female 8-week-old rats were enrolled in this study. In experimental groups, the disordered occlusion was created by moving the first molars mesially and the third ones distally. Immunohistochemistry and real-time PCR were performed at the end of the second or fourth week. RESULTS: Degenerative changes, characterized by interrupted continuity of hypertrophic layer, pyknotic and eosinophilic lesion with few nuclei, areas filled with eosinophilic nuclei, were observed in more joints from female experimental groups than male ones. However, thickening changes in hypertrophic layer were only found in male experimental groups. The gene expression of Col II, Col X and aggrecan increased in 4-wk male experimental subgroup (both P < 0.01), but decreased in 2-wk and 4-wk female subgroups (P < 0.05). The gene expression of ER? decreased in 2-wk male and female experimental subgroups (both P < 0.01), however, that of ER? increased except the 2-wk female experimental subgroup (all P < 0.01). The expression of aromatase decreased in both male and female experimental subgroups (all P<0.01). CONCLUSIONS: Mandibular condylar cartilage responses differently to the disordered occlusion in male and female rats. The levels of locally synthesized estrogen, ER? and ER? may have limited attribution, if any, to the sex-specific cartilage response.
Project description:Fusion of branchial arch derivatives is an essential event in the development of craniofacial architecture. A unique feature of the mandibular arch development is medial/lateral compartmentalization for the molecular networks. Those networks give rise to multiple region-specific organs, namely teeth, a tongue, salivary glands, and the supporting matrices such as bones and cartilages. We aimed to investigate molecular networks that govern the fusion process during mouse mandibular development. To this end, cDNA microarray technology was employed for screening of spatio-temporal gene expression in developing mandibular arch from E9.7 through E14.5.
Project description:Intermittent Parathyroid Hormone (I-PTH) is the only FDA approved anabolic drug therapy available for the treatment of osteoporosis in males and postmenopausal females. The effects of I-PTH on the chondrogenic lineage of the mandibular condylar cartilage (MCC) are not well understood. To investigate the role of I-PTH on the MCC and subchondral bone, we carried out our studies using 4 to 5 week old triple transgenic mice (Col1a1XCol2a1XCol10a1). The experimental group was injected with PTH (80??g/kg) daily for 2 weeks, while control group was injected with saline. Our histology showed that the I-PTH treatment led to an increased number of cells expressing Col1a1, Col2a1 and Col10a1. Additionally, there was an increase in cellular proliferation, increased proteoglycan distribution, increased cartilage thickness, increased TRAP activity, and mineralization. Immunohistochemical staining showed increased expression of pSMAD158 and VEGF in the MCC and subchondral bone. Furthermore our microCT data showed that I-PTH treatment led to an increased bone volume fraction, tissue density and trabecular thickness, with a decrease in trabecular spacing. Morphometric measurements showed increased mandibular length and condyle head length following I-PTH treatment. In conclusion, our study suggests that I-PTH plays a critical role in cellular proliferation, proteoglycan distribution, and mineralization of the MCC.