Zhuang Qianzhi, Li Bing, Wu Xiuping
Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, School and Hospital of Stomatology, Shanxi Medical University, Taiyuan, Shanxi, PR China.
Department of Stomatology, Weifang Hospital of Traditional Chinese Medicine, Weifang, Shandong, PR China.
J Dent Sci. 2023 Apr;18(2):626-635. doi: 10.1016/j.jds.2022.08.001. Epub 2022 Aug 30.
BACKGROUND/PURPOSE: Parathyroid hormone-related protein (PTHrP) is an important regulatory factor in the growth, development and remodeling of bone or cartilage, and acts through its sole receptor, parathyroid hormone receptor-1 (PTH1R). The present study aimed to research the expression changes of PTHrP, PTH1R and other relevant factors in condylar cartilage during the progress of temporomandibular joint osteoarthritis (TMJOA).
The animal model of TMJOA was constructed by the "resin-modified method", and Sprague Dawley (SD) rats were euthanized at 2 weeks, 4 weeks, 6 weeks and 8 weeks after occlusal elevation. The histological changes of condylar cartilage were observed by X-ray, hematoxylin-eosin (HE) and safranine O-fast green (SO-FG) staining. The expressions of PTHrP, PTH1R, Ki67, Collagen II (Col II), Collagen X (Col X) and Caspase 3 in each group were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).
TMJOA progression was time-dependent. In the experimental group, PTHrP expression was unimodal with a peak at 4 weeks, but PTH1R expression showed a decreasing trend. From 2 weeks to 8 weeks in the experimental group, Col X expression rather than Caspase 3 expression was negatively related to PTHrP's, which has no positive relation to Ki67 or Col II. These results demonstrated abnormal occlusal load may be an important pathogenic factor of TMJOA.
It may be one of the reasons of TMJOA progression that PTHrP can't play an effective role due to the low expression of PTH1R. PTHrP may be a direct factor regulating the hypertrophic differentiation of chondrocytes, but it does not directly regulate the proliferation and apoptosis of chondrocytes, and the realization of both regulatory effects may depend on the inhibition of hypertrophic differentiation.
背景/目的：甲状旁腺激素相关蛋白（PTHrP）是骨骼或软骨生长、发育和重塑过程中的重要调节因子，通过其唯一受体甲状旁腺激素受体-1（PTH1R）发挥作用。本研究旨在探讨颞下颌关节骨关节炎（TMJOA）进展过程中髁突软骨中PTHrP、PTH1R及其他相关因子的表达变化。
采用“树脂改良法”构建TMJOA动物模型，在咬合升高后2周、4周、6周和8周处死Sprague Dawley（SD）大鼠。通过X射线、苏木精-伊红（HE）和番红O-固绿（SO-FG）染色观察髁突软骨的组织学变化。采用定量实时聚合酶链反应（qRT-PCR）和免疫组织化学（IHC）检测各组中PTHrP、PTH1R、Ki67、Ⅱ型胶原（ColⅡ）、Ⅹ型胶原（ColⅩ）和半胱天冬酶3的表达。
TMJOA进展具有时间依赖性。实验组中，PTHrP表达呈单峰型，在4周时达到峰值，但PTH1R表达呈下降趋势。实验组从2周到8周，ColⅩ表达而非Caspase 3表达与PTHrP呈负相关，与Ki67或ColⅡ无正相关。这些结果表明异常咬合负荷可能是TMJOA的重要致病因素。
PTH1R低表达导致PTHrP无法发挥有效作用可能是TMJOA进展的原因之一。PTHrP可能是调节软骨细胞肥大分化的直接因子，但不直接调节软骨细胞的增殖和凋亡，这两种调节作用的实现可能依赖于对肥大分化的抑制。
