Abstract
Mandibular condylar cartilage (MCC) is a multi-zonal heterogeneous fibrocartilage containing different types of cells, but the factors/mechanisms governing the phenotypic transition across the zones have not been fully understood. The reliability of molecular studies heavily rely on the procurement of pure cell populations from the heterogeneous tissue. We used a combined laser-capture microdissection and microarray analysis approach which allowed identification of differential zone-specific gene expression profiling and altered pathways in the MCC of 5-week-old rats. The bioinformatics analysis demonstrated that the MCC cells clearly exhibited distinguishable phenotypes from the articular chondrocytes. Additionally, a set of genes has been determined as potential markers to identify each MCC zone individually; Crab1 gene showed the highest enrichment while Clec3a was the most downregulated gene at the superficial layer, which consists of fibrous (FZ) and proliferative zones (PZ). Ingenuity Pathway Analysis revealed numerous altered signaling pathways; Leukocyte extravasation signaling pathway was predicted to be activated at all MCC zones, in particular mature and hypertrophic chondrocytes zones (MZ&HZ), when compared with femoral condylar cartilage (FCC). Whereas Superpathway of Cholesterol Biosynthesis showed predicted activation in both FZ and PZ as compared with deep MCC zones and FCC. Determining novel zone-specific differences of large group of potential genes, upstream regulators and pathways in healthy MCC would improve our understanding of molecular mechanisms on regional (zonal) basis, and provide new insights for future therapeutic strategies.
Highlights
Mandibular condylar cartilage (MCC) is a multi-zonal heterogeneous fibrocartilage containing different types of cells, but the factors/mechanisms governing the phenotypic transition across the zones have not been fully understood
The mandibular condylar cartilage (MCC), a fibrocartilage layer that covers the mandibular condyle of Temporomandibular joint (TMJ), is multizonal in structure but it is unique in terms of cell phenotypes
Laser-Capture microdissection (LCM) sample was prepared by microdissecting the chondrocytes from the middle and deep zones of femoral condylar cartilage (FCC) tissue as a control (Supplementary Fig. 1b)
Summary
Mandibular condylar cartilage (MCC) is a multi-zonal heterogeneous fibrocartilage containing different types of cells, but the factors/mechanisms governing the phenotypic transition across the zones have not been fully understood. We used a combined laser-capture microdissection and microarray analysis approach which allowed identification of differential zone-specific gene expression profiling and altered pathways in the MCC of 5-week-old rats. Temporomandibular joint disorder (TMD) is a class of degenerative musculoskeletal conditions manifested as deformities in the morphology and function of the T MJ3,4 It includes abnormal position and/or structure of the TMJ disc and dysfunction of the associated musculature of the face (orofacial pain)[3,5]. Clinical management starts with noninvasive treatment modalities (physical therapy, occlusal splints, and prescription of pharmacologic agents), but for some patients other minimally invasive strategies (injections of sodium hyaluronate and/or corticosteroids, arthrocentesis, and arthroscopy) are considered[3] For those patients who show no improvement with the nonsurgical treatment modalities, open joint surgery may be carried out for discectomy, reshaping or reconstructing the articulating surfaces, and total joint replacement which is the most. Generating microarray data from LCM samples is feasible[9], such a combination should be capable of coping with several challenges[19,20]
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