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Transplantation of Parathyroid Hormone–Treated Achilles Tendon Promotes Meniscal Regeneration in a Rat Meniscal Defect Model
The American Journal of Sports Medicine ( IF 4.8 ) Pub Date : 2022-08-01 , DOI: 10.1177/03635465221112954
Kazuya Nishino 1 , Yusuke Hashimoto 2 , Yohei Nishida 3 , Kumi Orita 2 , Junsei Takigami 4 , Hiroaki Nakamura 2
Affiliation  

Background:

Autologous tendon grafts are used for meniscal reconstruction of surgically removed knee joint meniscus. However, as meniscal reconstruction cannot prevent the progression of cartilage degeneration, additional procedures that confer meniscus-like histological properties to the transplanted tendon are required for improved outcomes.

Hypotheses:

Parathyroid hormone (PTH)(1-34) induces cartilage formation in the rat tendon, and transplantation of PTH-treated tendon promotes meniscal regeneration.

Study Design:

Controlled laboratory study.

Methods:

Rat Achilles tendon–derived cells were cultured with or without PTH for 28 days and stained with Alcian blue to determine chondrogenic differentiation. After 14 and 28 days of incubation, gene expression was assessed using quantitative real-time polymerase chain reaction. In an in vivo study, rat Achilles tendon was injected with PTH and then transplanted onto a medial meniscal defect. Macroscopic and histological assessments of the regenerated meniscus and of cartilage degeneration in the tibial plateau were performed at 4 and 8 weeks after surgery.

Results:

In vitro, PTH-treated cells showed better staining with Alcian blue than the control (normal medium) group. PTH1R, Col2a1, Sox9, and RUNX2 were significantly upregulated in PTH-treated cells (P < .05). Macroscopically, the in vivo results revealed more prominent meniscal coverage and lesser progression of articular cartilage degeneration in the PTH group than in the phosphate-buffered saline–injected group. Histologically, toluidine blue staining revealed metachromasia in the PTH-injected tissue at 4 and 8 weeks. The PTH-treated regenerated meniscus showed positive immunostaining for type II collagen in the area exhibiting metachromasia. Moreover, PTH-treated tendon had an enhanced histological score compared with the untreated group at 4 and 8 weeks (P < .05).

Conclusion:

PTH(1-34) induced cartilage formation in the rat tendon. Transplantation of PTH(1-34)–treated Achilles tendon in a rat meniscal defect model induced meniscal regeneration and preserved knee articular cartilage. Macroscopically, PTH groups showed a greater coverage of the regenerated meniscus. Histologically, the regenerated meniscus had higher cartilaginous matrix content in rats transplanted with PTH-treated tendons. PTH(1-34) stimulated tendon-derived cells to promote chondrogenic differentiation.

Clinical Relevance:

Meniscal transplantation using PTH-injected autologous tendon grafts might promote meniscal regeneration and prevent progression of cartilage degeneration by stimulating chondrogenic differentiation of tendon-derived cells.



中文翻译:

甲状旁腺激素治疗的跟腱移植促进大鼠半月板缺损模型的半月板再生

背景:

自体肌腱移植物用于手术切除的膝关节半月板的半月板重建。然而,由于半月板重建不能阻止软骨退化的进展,因此需要额外的程序来赋予移植肌腱类似半月板的组织学特性以改善结果。

假设:

甲状旁腺激素 (PTH)(1-34) 在大鼠肌腱中诱导软骨形成,移植 PTH 治疗的肌腱可促进半月板再生。

学习规划:

受控实验室研究。

方法:

将大鼠跟腱衍生细胞在有或没有 PTH 的情况下培养 28 天,并用阿尔新蓝染色以确定软骨分化。孵育 14 天和 28 天后,使用定量实时聚合酶链反应评估基因表达。在一项体内研究中,大鼠跟腱注射了 PTH,然后移植到内侧半月板缺损处。在手术后 4 周和 8 周对再生半月板和胫骨平台软骨退变进行宏观和组织学评估。

结果:

在体外,PTH 处理的细胞显示出比对照组(正常培养基)更好的阿尔新蓝染色。PTH1R、Col2a1、Sox9 和 RUNX2 在 PTH 处理的细胞中显着上调(P < .05)。从宏观上看,体内结果显示,与磷酸盐缓冲盐水注射组相比,PTH 组的半月板覆盖率更高,关节软骨退化的进展更慢。组织学上,甲苯胺蓝染色显示 PTH 注射组织在 4 周和 8 周时出现异染。经 PTH 处理的再生半月板在异染区域显示出 II 型胶原蛋白的阳性免疫染色。此外,在第 4 周和第 8 周,与未治疗组相比,PTH 治疗组的肌腱组织学评分有所提高(P < .05)。

结论:

PTH(1-34) 在大鼠肌腱中诱导软骨形成。在大鼠半月板缺损模型中移植经 PTH(1-34) 处理的跟腱可诱导半月板再生并保留膝关节软骨。从宏观上看,PTH 组显示出更大的再生半月板覆盖率。组织学上,在移植了 PTH 处理的肌腱的大鼠中,再生的半月板具有更高的软骨基质含量。PTH(1-34) 刺激肌腱衍生细胞促进软骨分化。

临床相关性:

使用注射 PTH 的自体肌腱移植物进行半月板移植可能会通过刺激肌腱衍生细胞的软骨分化来促进半月板再生并防止软骨退化的进展。

更新日期:2022-08-01
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