School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States.
Penn-CHOP Lung Biology Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Penn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Division of Pediatric Cardiology, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States.
Acta Biomater. 2024 Nov;189:192-207. doi: 10.1016/j.actbio.2024.09.046. Epub 2024 Oct 1.
Understanding matrix molecular activities that regulate the postnatal growth and remodeling of the temporomandibular joint (TMJ) articular disc and condylar cartilage will enable the development of effective regenerative strategies targeting TMJ disorders. This study elucidated the distinct roles of type V collagen (collagen V) in regulating these two units. Studying the TMJ of young adult Col5a1 mice, we found that loss of collagen V resulted in substantial changes in the proliferation, clustering and density of progenitors in condylar cartilage, but did not have a major impact on disc cells that are more fibroblast-like. Although loss of collagen V led to thickened collagen fibrils with increased heterogeneity in the disc, there were no significant changes in local micromodulus, except for a reduction at the posterior end of the inferior side. Following the induction of aberrant occlusal loading by the unilateral anterior crossbite (UAC) procedure, both wild-type (WT) and Col5a1 condylar cartilage exhibited salient remodeling, and Col5a1 condyle developed more pronounced degeneration and tissue hypertrophy at the posterior end than the WT. In contrast, neither UAC nor collagen V deficiency induced marked changes in the morphology or biomechanical properties of the disc. Together, our findings highlight the distinct roles of collagen V in regulating these two units during postnatal growth and remodeling, emphasizing its more crucial role in condylar cartilage due to its impact on the highly mechanosensitive progenitors. These results provide the foundation for using collagen V to improve the regeneration of TMJ and the care of patients with TMJ disorders. STATEMENT OF SIGNIFICANCE: Successful regeneration of the temporomandibular joint (TMJ) articular disc and condylar cartilage remains a significant challenge due to the limited understanding of matrix molecular activities that regulate the formation and remodeling of these tissues. This study demonstrates that collagen V plays distinct and critical roles in these processes. In condylar cartilage, collagen V is essential for regulating progenitor cell fate and maintaining matrix integrity. In the disc, collagen V also regulates fibril structure and local micromechanics, but has a limited impact on cell phenotype or its remodeling response. Our findings establish collagen V as a key component in maintaining the integrity of these two units, with a more crucial role in condylar cartilage due to its impact on progenitor cell activities.
了解调节颞下颌关节（TMJ）关节盘和髁突软骨出生后生长和重塑的基质分子活动将使针对 TMJ 疾病的有效再生策略的发展成为可能。本研究阐明了 V 型胶原（胶原 V）在调节这两个单位中的独特作用。研究年轻成年 Col5a1 小鼠的 TMJ 时，我们发现胶原 V 的缺失导致髁突软骨中祖细胞的增殖、聚集和密度发生重大变化，但对更呈纤维母细胞样的盘细胞没有重大影响。尽管胶原 V 的缺失导致盘状胶原纤维变厚，异质性增加，但局部微硬度除了在下侧后端减少外，没有明显变化。在单侧前交叉咬合（UAC）程序引起异常咬合负荷后，WT 和 Col5a1 髁突软骨都表现出明显的重塑，并且 Col5a1 髁突在后端比 WT 发展出更明显的退行性变和组织肥大。相比之下，UAC 或胶原 V 缺乏均未引起盘状形态或生物力学特性的明显变化。总之，我们的研究结果强调了胶原 V 在出生后生长和重塑过程中调节这两个单位的独特作用，由于其对高度机械敏感祖细胞的影响，强调了其在髁突软骨中的更关键作用。这些结果为使用胶原 V 改善 TMJ 的再生和 TMJ 疾病患者的护理提供了基础。
由于对调节这些组织形成和重塑的基质分子活动的了解有限，成功再生颞下颌关节（TMJ）关节盘和髁突软骨仍然是一个重大挑战。本研究表明，胶原 V 在这些过程中发挥独特且关键的作用。在髁突软骨中，胶原 V 对于调节祖细胞命运和维持基质完整性至关重要。在盘状中，胶原 V 也调节纤维结构和局部微力学，但对细胞表型或其重塑反应的影响有限。我们的研究结果确立了胶原 V 作为维持这两个单位完整性的关键组成部分，由于其对祖细胞活动的影响，在髁突软骨中具有更关键的作用。
