Experimental Surgery and Regenerative Medicine, Department of Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany.
Orthopaedic Center of People's Liberation Army, Xiamen University Affiliated Southeast Hospital, Zhangzhou, China.
Cell Death Dis. 2017 Oct 12;8(10):e3116. doi: 10.1038/cddis.2017.510.
Tenomodulin (Tnmd) is the best-known mature marker for tendon and ligament lineage cells. It is important for tendon maturation, running performance and has key implications for the resident tendon stem/progenitor cells (TSPCs). However, its exact functions during the tendon repair process still remain elusive. Here, we established an Achilles tendon injury model in a Tnmd knockout (Tnmd) mouse line. Detailed analyses showed not only a very different scar organization with a clearly reduced cell proliferation and expression of certain tendon-related genes, but also increased cell apoptosis, adipocyte and blood vessel accumulation in the early phase of tendon healing compared with their wild-type (WT) littermates. In addition, Tnmd tendon scar tissue contained augmented matrix deposition of biglycan, cartilage oligomeric matrix protein (Comp) and fibronectin, altered macrophage profile and reduced numbers of CD146-positive cells. In vitro analysis revealed that Tnmd TSPCs exhibited significantly reduced migration and proliferation potential compared with that of WT TSPCs. Furthermore, Tnmd TSPCs had accelerated adipogenic differentiation accompanied with significantly increased peroxisome proliferator-activated receptor gamma (Pparγ) and lipoprotein lipase (Lpl) mRNA levels. Thus, our results demonstrate that Tnmd is required for prevention of adipocyte accumulation and fibrovascular scar formation during early tendon healing.
腱调蛋白（Tnmd）是肌腱和韧带谱系细胞的最知名的成熟标志物。它对于肌腱成熟、跑步表现非常重要，对驻留的肌腱干/祖细胞（TSPCs）有重要影响。然而，它在肌腱修复过程中的确切功能仍然难以捉摸。在这里，我们在 Tnmd 敲除（Tnmd）小鼠品系中建立了跟腱损伤模型。详细分析不仅显示出非常不同的瘢痕组织，细胞增殖和某些肌腱相关基因的表达明显减少，而且与野生型（WT）同窝仔相比，在肌腱愈合的早期阶段，细胞凋亡、脂肪细胞和血管积累增加。此外，Tnmd 肌腱瘢痕组织中大聚集蛋白聚糖、软骨寡聚基质蛋白（Comp）和纤连蛋白的基质沉积增加，巨噬细胞表型改变，CD146 阳性细胞数量减少。体外分析显示，与 WT TSPCs 相比，Tnmd TSPCs 的迁移和增殖潜力显著降低。此外，Tnmd TSPCs 的脂肪生成分化加速，过氧化物酶体增殖物激活受体γ（Pparγ）和脂蛋白脂肪酶（Lpl）mRNA 水平显著升高。因此，我们的结果表明，Tnmd 对于预防早期肌腱愈合过程中的脂肪细胞积累和纤维血管瘢痕形成是必需的。
