Development Of Mandibular Condylar Cartilage Research Articles

Formation of the Mandibular Condylar Cartilage in Human Specimens Between 10 and 15 Weeks of Gestation

Background: The study examines some morphological and histological factors that may contribute to condylar cartilage (CC) formation. The specimens used were consecutive sections obtained from 20 human fetuses ranging in age from 10 to 15 weeks. The vascular canals (VC) emerge in the CC and initiate the process of intramembranous ossification. The mandibular condylar cartilage is crucial for the growth and function of the mandible, and it also contributes to the development of the Temporomandibular joint. Understanding the development of mandibular condylar cartilage throughout the early stages of gestation is essential for detecting congenital craniofacial deformities. Objectives: Examine the stages of MCC development in human samples from fetuses at 10-15 weeks of gestation. Study Design: A descriptive Cross-sectional Study. Place and Duration of Study: Department of Anatomy and Obstetric Nowshera Medical College from 15th Nov 2020 to 1st Jun 2021. The changes in the shape and size of the bones and the processes of bone formation should also be determined. Methods: The current study is descriptive, cross-sectional, and involves post-mortem human fetal specimens aged 10-15 weeks. The specimens were obtained from the Department of Obstetrics of QHAMC after miscarriages and intrauterine deaths. The absence of external and congenital malformations was verified. Light microscopic and histological assessment was done with the aid of H&E-stained sections. Results : Twenty fetal specimens were used in the study, with an average gestation period of 12. 5 weeks (±1. 5 weeks). Histological analysis revealed gradual chondrocyte maturation and the beginning of the ossification process. At ten weeks, MCC was comprised of undifferentiated mesenchymal cells. At twelve weeks, it is possible to observe the differentiation of chondrocytes and early ossification. At 15 weeks, the ossification stages of the CRL were at a superior level with the hypertrophic chondrocytes and mineralized cartilage. The p-values for differences in developmental stages between the gestational ages were less than 0. Hence, the differences were statistically significant. Conclusion: The MCC in human specimens at 10–15 weeks' gestation undergoes considerable morphological transformation and commences the ossification process. Knowledge of these stages is essential in identifying and intervening in congenital craniofacial disorders. The authors recommend that future studies focus on investigating molecular processes that may contribute to the development of MCC. Keywords: Mandibular condylar cartilage, Development, Gestation, Ossification

Primary observation of the role of posttranslational modification of dentin sialophosphoprotein (DSPP) on postnatal development of mandibular condyle in mice

ObjectivesWe aimed to observe the posttranslational role of dentin sialophosphoprotein (DSPP) on postnatal development of mandibular condyle in mice. MethodsTo explore the function of full-length DSPP, four groups of mice were employed: (1) wild type (WT) mice; (2)Dspp knockout (Dspp KO) mice; (3) mice expressing the normal DSPP transgene in the Dspp KO background (Dspp KO/normal Tg); (4) mice expressing the uncleavable full-length DSPP in the Dspp KO background (Dspp KO/D452A Tg). Firstly, Plain X-ray Radiography and Micro-computed Tomography were used to observe the condylar morphology changes of Dspp KO/D452A Tg mice in comparison with the other three groups. Then, Hematoxylin & eosin and toluidine blue staining were applied to uncover the histological changes of mandibular condylar cartilage (MCC) of Dspp KO/D452A Tg mice. To explore the function of the NH2-terminal fragments (i.e. DSP/DSP-PG), three groups of mice were employed: (1) WT mice; (2) Dspp KO mice; (3) mice expressing the NH2-terminal fragments of DSPP in the Dspp-null background (Dspp KO/DSP Tg). The former strategies were utilized to examine the differences of condylar morphology and histological structures changes within three groups of mice. ResultsTransgenic full-length DSPP partially maintained mandibular condylar morphology and MCC thickness of Dspp KO mice. Transgenic DSP failed to do so, but led to smaller mandibular condyle and disordered cartilage structure. ConclusionsOur observations provide insight into the role of posttranslational modification of DSPP in the postnatal development of healthy MCC and maintenance of condylar morphology.

Advances in research of microRNA in the growth and development of mandibular condyle cartilage

MicroRNA (miRNA) are a class of small non-coding single-stranded RNA that exert their biological effects by binding to target messenger RNA (mRNA). There is new evidence that miRNA may play an important role in regulating the growth and development of mandibular condylar cartilage. In this paper, the production and mechanism of miRNA are reviewed, and the progress of studies on the growth and development of mandibular condylar cartilage, which is helpful to further study the growth and development of mandibular condylar cartilage.

The Zonal Architecture of the Mandibular Condyle Requires ADAMTS5

Temporomandibular joint (TMJ) osteoarthritis (TMJOA) disrupts extracellular matrix (ECM) homeostasis, leading to cartilage degradation. Upregulated a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)–5 leads to cleavage of its substrate aggrecan (Acan) and is considered a hallmark of TMJOA. However, most research on ADAMTS5-Acan turnover has focused on hyaline cartilage, not fibrocartilage, which comprises the TMJ. The mandibular condylar cartilage (MCC) of the TMJ is organized in zones, and chondrocytes are arranged in axial rows, yet the molecular mechanisms required to generate the MCC zonal architecture have not been elucidated. Here, we test the hypothesis that ADAMTS5 is required for development of the TMJ MCC. Adamts5+/+ and Adamts5–/– murine TMJs were harvested at postnatal day 7 (P7), P21, 2 mo, and 6 mo of age; histomorphometrics indicated increased ECM. Immunohistochemistry and Western blots demonstrated the expanded ECM correlated with increased Acan localization in Adamts5–/– compared to Adamts5+/+. Cell volume was also decreased in the MCC of Adamts5–/– due to both a reduction in cell size and less mature hypertrophic chondrocytes. Analysis of chondrogenic maturation markers by quantitative real-time polymerase chain reaction indicated Col2a1, Col10a1, and Sox9 were significantly reduced in Adamts5–/– MCC compared to that of Adamts5+/+. The older (6 mo) Adamts5–/– MCC exhibited changes in chondrogenic cell arrangements, including clustering and chondrogenic atrophy, that correlated with early stages of TMJOA using modified Mankin scoring. These data indicate a potentially novel and critical role of ADAMTS5 for maturation of hypertrophic chondrocytes and establishment of the zonal architecture that, when disrupted, may lead to early onset of TMJOA.

Spatial and temporal expression of Smad signaling members during the development of mandibular condylar cartilage.

The present study aimed to explore the underlying developmental mechanism of mothers against decapentaplegic homolog (Smad) signaling in the development of mandibular condylar cartilage. To achieve this, the expression levels of Smad2, 3, 4 and 7, and phosphorylated Smad2/3 were investigated at different time points in developing mandibular condylar cartilage. Mandibular condyles from C57BL/6J mice were dissected at the prenatal and postnatal stages. Serial sections were made and the distributions of Smad proteins were examined using immunohistochemical techniques intermittently between day 14.5 of gestation and postnatal day 7. All Smad proteins examined in the present study were expressed in the condylar blastema and during early chondrogenesis. At the postnatal stage, Smad2 and 4 were localized in proliferative and mineralized hypertrophic chondrocytes. Smad3 and 7 were expressed in proliferative and hypertrophic chondrocytes, including pre-hypertrophic and mineralized hypertrophic chondrocytes. Later, positive immunoreactivity of Smad3 reduced at postnatal day 7. A similar expression pattern to Smad3 was observed for p-Smad2/3, but p-Smad2/3 was located in the nuclei of proliferative chondrocytes. These results suggest that Smad signaling members are involved in the development of mandibular condylar cartilage. In addition, the spatial and temporal expression of these Smads indicate that Smad signaling is involved in regulating the differentiation of chondrocytes and endochondral ossification, in order to maintain normal chondrogenesis and morphogenesis of mandibular condylar cartilage.

Spatio-temporal expression patterns of Wnt signaling pathway during the development of temporomandibular condylar cartilage

There is a growing body of evidence supporting the involvement of the Wnt signaling pathway in various aspects of skeletal and joint development; however, it is unclear whether it is involved in the process of temporomandibular joint development. In order to clarify this issue, we examined the spatio-temporal distribution of mRNAs and proteins of the Wnt family during the formation of the mandibular condylar cartilage at the prenatal and postnatal stages. An in situ hybridization test revealed no mRNAs of β-catenin and Axin2 during early mesenchymal condensation; the ligands surveyed in this study (including Wnt-4, 5a, and 9a) were clearly detected at various ranges of expression, mainly in the condylar blastema and later distinct cartilaginous layers. Apart from β-catenin and Axin2, the Wnt family members surveyed in this study, including Lef-1, were found to be immunopositive during early chondrogenesis in the condylar cartilage at E14.5. After distinct chondrocyte layers were identified within the cartilage at E16.5, the expression of the Wnt signaling members was different and mainly restricted to proliferating cells and mineralized hypertrophic chondrocytes. In the adult mandibular condylar cartilage, the Wnt-4 mRNA, as well as the Wnt-4 and Wnt-9a proteins, was not observed. Our findings demonstrated that the Wnt signaling pathway was associated with the development of mandibular condylar cartilage.

Quantitative Proteomic Analysis of Rat Condylar Chondrocytes during Postnatal Development.

To investigate differentially expressed proteins in rat mandibular condylar cartilage (MCC) chondrocytes caused by initial mastication for short postnatal periods. Four groups of protein samples were extracted from primary cultured rat MCC chondrocytes, harvested from eigthy postnatal SD rats aged 1,7,14 and 28 days, with twenty in each group. Total proteins were labelled with isobaric tags for relative and absolute quantification (iTRAQ) reagents. Two-dimensional nano-high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization-time-of-flight/ time-of-flight (MALDI-TOF/TOF) mass spectrometry analysis with iTRAQ technique were performed. All data were analysed by MASCOT software with the SWISSPROT protein database. Furthermore, bioinformatics and statistical analysis were performed to classify their cellular components, biological processes, molecular functions and metabolic pathway by the PANTHER database. In total, 137 differentially expressed proteins were identified during MCC growth and were assigned to one or more cellular components. According to the PANTHER analysis, a significant proportion of proteins are involved in the metabolic process, cellular process, biological regulation, developmental process and response to stimulus. The most extensive molecular function was 43% in catalytic activity. In addition, it was found that proteins in MCC chondrocytes change markedly on the growth stage of eruption of the teeth. This study provides an integrated perspective of molecular mechanisms regulating early normal postnatal growth and development of rat MCC at the protein level.

Fetal jaw movement affects Ihh signaling in mandibular condylar cartilage development: The possible role of Ihh as mechanotransduction mediator

ObjectiveJaw movement is an important mechanical factor for prenatal development of the condylar cartilage of mandible. Fetal jaw movement restriction has been shown to cause deformity of the mandibular condyle. We hypothesized that this treatment affects the expression of mechanosensitive molecules, namely Indian hedgehog (Ihh) and Parathyroid hormone related protein (PTHrP) in the condyle. Experimental methodsWe restrained jaw movement by suturing the jaw of E15.5 mouse embryos and allowed them to develop until E18.5 using exo utero system, and analyzed them by immunohistochemistry and in situ hybridization methods. ResultsMorphological, histomorphometric and immunohistochemical study showed that the mandibular condylar cartilage was reduced and deformed, the volume and total cell numbers in the condylar cartilage were also reduced, and number and/or distribution of 5-bromo-2′-deoxyuridine-positive cells, Ihh-positive cells in the mesenchymal and pre-hypertrophic zones were significantly and correspondingly decreased in the sutured group. Using in situ hybridization, reduced expression of Ihh, PTHrP and their related receptors were observed in condylar cartilage of the sutured embryos. ConclusionsOur results revealed that the altered mechanical stress induced by prenatal jaw movement restriction decreased proliferating cells, the amount of cartilage, and altered expression of the Ihh and PTHrP, suggesting that Ihh act as mechanotransduction mediators in the development of mandibular condylar cartilage.

Expression of Ten‐m/Odz3 in the fibrous layer of mandibular condylar cartilage during postnatal growth in mice

It has been speculated that the mandibular condyle develops via the differentiation of the fibroblast-like cells covering the condyle into chondrocytes; however, the developmental mechanisms behind this process have not been revealed. We used laser-capture microdissection and cDNA microarray analysis to elucidate the genes that are highly expressed in these fibroblast-like cells. Among these genes, the transcription of Ten-m/Odz3 was significantly increased in the fibroblast-like cells compared with other cartilage tissues. For the first time, we describe the temporal and spatial expression of Ten-m/Odz3 mRNA in relation to the expression of type I, II, and X collagen mRNA, as determined by in-situ hybridization in mouse mandibular condylar cartilage and mouse femoral cartilage during the early stages of development. Ten-m/Odz3 was expressed in the fibrous layer and the proliferating and mature chondrocyte layers, which expressed type I and II collagen, respectively, but was not detected in the hypertrophic chondrocyte layer. Furthermore, we evaluated the in-vitro expression of Ten-m/Odz3 using ATDC5 cells, a mouse chondrogenic cell line. Ten-m/Odz3 was expressed during the early stage of the differentiation of mesenchymal cells into chondrocytes. These findings suggest that Ten-m/Odz3 is involved in the differentiation of chondrocytes and that it acts as a regulatory factor in the early stages of the development of mandibular condylar cartilage.

Type II collagen and TGF-betas in developing and aging porcine mandibular condylar cartilage: immunohistochemical studies.

Transforming growth factor-betas (TGF-betas) have been associated with the development and maintenance of articular cartilage. However, no studies have addressed their role in the postnatal development of mandibular condylar cartilage. This investigation represents the first immunohistochemical characterization of TGF-beta isoforms and type II collagen in porcine mandibular condylar cartilage from various age groups. Furthermore, it is the first description of possible age-related changes in the expression of these proteins during postnatal development of this tissue. Condylar cartilage was dissected from freshly harvested temporomandibular joints of newborn, 6-, 12-, 24-, and 36-month-old farm swine. TGF-beta1, TGF-beta2, TGF-beta3, and type II collagen were localized via standard immunohistochemical procedures. An immunoblot technique was employed to compare the relative amount of each protein present in the various age groups. Immunoreactivity was detected in mandibular condylar cartilage for all three isoforms of TGF-beta and for Type II collagen. All age groups demonstrated some evidence of immunostaining, primarily in the cytoplasm of cells from most zones of the cartilage. Immunoblot results indicated that TGF-beta isoforms had individualized patterns of expression. When newborn protein levels were taken as the baseline, TGF-beta1 demonstrated a significant increase at ages 24 and 36 months. TGF-beta2 significantly increased at 6, 12, 24, and 36 months (peak levels at 24 months; similar levels at 6, 12, and 36 months), whereas TGF-beta3 remained stable at all ages. Type II collagen demonstrated increases that paralleled the increased levels of TGF-beta1 and TGF-beta2 at 24 and 36 months.