1 Departments of Periodontics and Oral Medicine, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
2 Department of Prosthetic Dental Sciences, College of Dentistry, King Saud University, Riyadh, Saudi Arabia.
J Dent Res. 2018 Mar;97(3):321-328. doi: 10.1177/0022034517738190. Epub 2017 Oct 26.
Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints. To assess the requirement for Ddr2 in TMJ development, studies were undertaken to compare wild-type and smallie ( slie) mice, which contain a spontaneous deletion in Ddr2 to produce an effective null allele. Analysis of TMJs from newborn Ddr2 mice revealed a developmental delay in condyle mineralization, as measured by micro-computed tomography and histologic analysis. In marked contrast, knee joints of Ddr2 mice were normal. Analysis of older Ddr2 mice (3 and 10 mo) revealed that the early developmental delay led to a dramatic and progressive loss of TMJ articular integrity and osteoarthritis-like changes. Mutant condyles had a rough and flattened bone surface, accompanied by a dramatic loss of bone mineral density. Mankin scores showed significantly greater degenerative changes in the TMJs of 3- and 10-mo-old Ddr2 mice as compared with wild-type controls. No DDR2-dependent degenerative changes were seen in knees. Analysis of primary cultures of TMJ articular chondrocytes from wild-type and Ddr2 mice showed defects in chondrocyte maturation and mineralization in the absence of Ddr2. These studies demonstrate that DDR2 is necessary for normal TMJ condyle development and homeostasis and that these DDR2 functions are restricted to TMJ fibrocartilage and not seen in the hyaline cartilage of the knee.
颞下颌关节（TMJ）疾病通常与下颌骨髁的骨关节炎样变化的发展有关。盘状结构域受体 2（DDR2）是一种胶原受体，优先被 TMJ 和其他纤维软骨中的 I 型和 III 型胶原激活，与 TMJ 退变有关，但它在正常关节发育中的作用尚未被研究过。使用 Ddr2 LacZ 标记的小鼠和免疫组织化学方法，我们发现 DDR2 优先在 TMJ 的关节区表达和激活，而不在膝关节表达和激活。为了评估 Ddr2 在 TMJ 发育中的必要性，我们比较了野生型和小型（s lie）小鼠，后者在 Ddr2 中含有自发缺失，从而产生有效的无效等位基因。对新生 Ddr2 小鼠的 TMJ 分析显示，下颌骨髁矿化发育延迟，通过微计算机断层扫描和组织学分析测量。相比之下，Ddr2 小鼠的膝关节正常。对年龄较大的 Ddr2 小鼠（3 个月和 10 个月）的分析表明，早期发育延迟导致 TMJ 关节完整性的显著和进行性丧失以及骨关节炎样变化。突变的髁突骨表面粗糙且扁平，伴有骨密度的显著丧失。Mankin 评分显示，与野生型对照相比，3 个月和 10 个月大的 Ddr2 小鼠的 TMJ 退行性变化明显更大。在膝关节中没有观察到 DDR2 依赖性的退行性变化。对来自野生型和 Ddr2 小鼠的 TMJ 关节软骨原代培养物的分析表明，在没有 DDR2 的情况下，软骨细胞成熟和矿化存在缺陷。这些研究表明，DDR2 是正常 TMJ 髁突发育和稳态所必需的，并且这些 DDR2 功能仅限于 TMJ 纤维软骨，而在膝关节的透明软骨中未见。
