University of Illinois at Chicago, Department of Oral Biology, Chicago, IL, USA.
Tokyo Dental College, Department of Fixed Prosthodontics, Tokyo, Japan.
Sci Rep. 2019 Jan 11;9(1):56. doi: 10.1038/s41598-018-37028-1.
The degeneration of articular cartilage underscores the clinical pathology of temporomandibular joint osteoarthritis (TMJ-OA) and is promoted through dysfunctional biochemical or biophysical signaling. Transduction of these signals has a multifaceted regulation that includes important cell-matrix derived interactions. The matrix encapsulating the cells of the mandibular condylar cartilage (MCC) is rich in type VI collagen. Neuron/glia antigen 2 (NG2) is a type I transmembrane proteoglycan that binds with type VI collagen. This study defines the temporospatial dynamics of NG2-type VI collagen interactions during the progression of TMJ-OA. Membrane-bound NG2 is found to colocalize with pericellular type VI collagen in superficial layer cells in the MCC perichondrium but is present at high levels in the cytosol of chondroblastic and hypertrophic cells. When TMJ -OA is induced using a surgical instability model, localized disruptions of pericellular type VI collagen are observed on the central and medial MCC and are associated with significantly higher levels of cytosolic NG2. NG2 localized within the cytosol is found to be transported through clathrin and dynamin mediated endocytic pathways. These findings are consistent with NG2 behavior in other injury models and underscore the potential of NG2 as an entirely novel molecular mechanism of chondrocyte function contextually linked with TMJ-OA.
关节软骨的退化突出了颞下颌关节骨关节炎（TMJ-OA）的临床病理学，并通过功能失调的生化或生物物理信号促进。这些信号的转导具有多方面的调节，包括重要的细胞-基质衍生的相互作用。包围下颌髁突软骨（MCC）细胞的基质富含 VI 型胶原。神经胶质抗原 2（NG2）是一种 I 型跨膜蛋白聚糖，与 VI 型胶原结合。这项研究定义了 NG2-VI 型胶原相互作用在 TMJ-OA 进展过程中的时空动态。膜结合的 NG2 被发现与 MCC 软骨膜浅层细胞的细胞周 VI 型胶原共定位，但在软骨母细胞和肥大细胞的细胞质中存在高水平。当使用手术不稳定模型诱导 TMJ-OA 时，观察到中央和内侧 MCC 的细胞周 VI 型胶原局部破坏，并与细胞质 NG2 水平显著升高相关。发现位于细胞质内的 NG2 通过网格蛋白和动力蛋白介导的内吞途径运输。这些发现与其他损伤模型中的 NG2 行为一致，并强调了 NG2 作为一种全新的分子机制的潜力，该机制与 TMJ-OA 相关联，与上下文相关联。
