期刊
MATRIX BIOLOGY
卷 102, 期 -, 页码 1-19出版社
ELSEVIER
DOI: 10.1016/j.matbio.2021.07.002
关键词
Type V collagen; Cartilage matrix; Temporomandibular joint; Mechanobiology; Collagen fibrils; Ehlers-Danlos syndrome
资金
- National Science Foundation (NSF) [CMMI-1751898]
- National Institutes of Health (NIH) [R21DE029567]
- NIH [P30AR069619]
- NSF [NNCI-1542153]
This study investigates the role of type V collagen in post-natal growth of temporomandibular joint (TMJ) condylar cartilage, revealing its impact on tissue structure, cell proliferation, and mechanoregulation of progenitor cell activities. Loss of type V collagen leads to abnormal tissue development, reduced cell density, and limited progenitor cell proliferation, highlighting the significance of type V collagen in regulating TMJ condylar cartilage growth.
This study queried the role of type V collagen in the post-natal growth of temporomandibular joint (TMJ) condylar cartilage, a hybrid tissue with a fibrocartilage layer covering a secondary hyaline cartilage layer. Integrating outcomes from histology, immunofluorescence imaging, electron microscopy and atomic force microscopy-based nanomechanical tests, we elucidated the impact of type V collagen reduction on TMJ condylar cartilage growth in the type V collagen haploinsufficiency and inducible knockout mice. Reduction of type V collagen led to significantly thickened collagen fibrils, decreased tissue modulus, reduced cell density and aberrant cell clustering in both the fibrous and hyaline layers. Post-natal growth of condylar cartilage involves the chondrogenesis of progenitor cells residing in the fibrous layer, which gives rise to the secondary hyaline layer. Loss of type V collagen resulted in reduced proliferation of these cells, suggesting a possible role of type V collagen in mediating the progenitor cell niche. When the knockout of type V collagen was induced in post-weaning mice after the start of physiologic TMJ loading, the hyaline layer exhibited pronounced thinning, supporting an interplay between type V collagen and occlusal loading in condylar cartilage growth. The phenotype in hyaline layer can thus be attributed to the impact of type V collagen on the mechanically regulated progenitor cell activities. In contrast, knee cartilage does not contain the progenitor cell population at post-natal stages, and develops normal structure and biomechanical properties with the loss of type V collagen. Therefore, in the TMJ, in addition to its established role in regulating the assembly of collagen I fibrils, type V collagen also impacts the mechanoregulation of progenitor cell activities in the fibrous layer. We expect such knowledge to establish a foundation for understanding condylar cartilage matrix development and regeneration, and to yield new insights into the TMJ symptoms in patients with classic Ehlers-Danlos syndrome, a genetic disease due to autosomal mutation of type V collagen. (c) 2021 Elsevier B.V. All rights reserved.
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