Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Faculty of Life Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Osteoarthritis Cartilage. 2011 Jul;19(7):886-94. doi: 10.1016/j.joca.2011.04.007. Epub 2011 Apr 23.
We studied the effects of the transient activation of parathyroid hormone (PTH)/PTH-related peptide (PTHrP) signaling during the repair of 5-mm-diameter full-thickness defects of articular cartilage in the rabbit.
Cylindrical full-thickness articular cartilage defects of 5mm in diameter were artificially created in the femoral trochlea of male adolescent Japanese white rabbits using a hand-drill. Recombinant human PTH(1-84) was then administered into the joint cavity continuously or intermittently for 2 weeks post-injury. The reparative tissues were histologically examined at 2, 4, and 8 weeks, and were also immunohistochemically examined for type II collagen. Double immunostaining analysis was also performed for the PTH/PTHrP receptor and proliferating cell nuclear antigen (PCNA) in the regenerating tissues.
No evidence of cartilage formation was evident throughout the period of the experiments in injured animals administered saline alone. In contrast, cartilage formation occurred at 4 weeks in both the continuous and intermittent PTH-treated defects. At 8 weeks post-injury, for the intermittently treated defects, the regenerated cartilage successfully resurfaced the defects and the original bone-articular cartilage junction was recovered. In contrast, the defects were covered with fibrous or fibrocartilaginous tissues in the continuously administered group. PCNA and PTH/PTHrP receptor-double positive mesenchymal cells were significantly increased in both the continuous and intermittent PTH-treated defects at 2 weeks post-injury.
The present results suggest that the transient activation and release from PTH/PTHrP signaling during the early stages of the cartilage repair process facilitates the induction of regenerative chondrogenesis in full-thickness articular cartilage defects.
我们研究了甲状旁腺激素（PTH）/甲状旁腺激素相关肽（PTHrP）信号短暂激活对兔关节软骨全层 5mm 直径缺损修复的影响。
使用手动钻头在雄性青少年日本白兔的股骨滑车中人工制造直径为 5mm 的圆柱形全层关节软骨缺损。损伤后 2 周内，持续或间歇地将重组人 PTH(1-84)注入关节腔。在 2、4 和 8 周时对修复组织进行组织学检查，并对 II 型胶原进行免疫组织化学检查。还对再生组织中的 PTH/PTHrP 受体和增殖细胞核抗原（PCNA）进行双免疫染色分析。
单独给予生理盐水的损伤动物在整个实验期间均未出现软骨形成的证据。相比之下，连续和间歇 PTH 治疗的缺损在 4 周时均出现软骨形成。损伤后 8 周，间歇治疗的缺损中，再生软骨成功覆盖了缺陷，并且恢复了原始的骨-关节软骨交界处。相比之下，连续给药组的缺陷被纤维或纤维软骨组织覆盖。损伤后 2 周，连续和间歇 PTH 治疗的缺损中，PCNA 和 PTH/PTHrP 受体双阳性间充质细胞显著增加。
本研究结果表明，在软骨修复过程的早期阶段，PTH/PTHrP 信号的短暂激活和释放有助于全层关节软骨缺损中再生性软骨生成的诱导。
