Arnesen Solfrid M, Lawson Moira A
Department of Food Science, Royal Veterinary and Agricultural University, Rolighedsvej 30, 1958 Frederiksberg C, Denmark.
Mech Ageing Dev. 2006 Sep;127(9):726-32. doi: 10.1016/j.mad.2006.05.003. Epub 2006 Jun 15.
During aging the increase in collagen cross-linking and total amount of collagen in tendon leads to a decline in both its flexibility and its ability to heal after injury. Fibroblasts are responsible for the synthesis of the macromolecules that constitute tendonous tissue. The ability of fibroblasts to maintain tissue homeostasis is compromised with increasing age underlying many of the age-related pathologies of the musculoskeletal system. This leads to a slowdown in connective tissue healing. Whether these deficits are due to changes in connective tissue, structure or to changes in tendon fibroblast function is unknown. We show that tendon fibroblasts from old mice have an altered morphology, reduced level of function, and exhibit changes in protein transport, compared to fibroblasts from young mice. The fibroblasts from old mice are not senescent, they are distinct phenotypes. Achilles tendon fibroblasts from old mice have low motility and proliferation, a poorly organised actin cytoskeleton and a different localisation of key focal adhesion proteins compared to the same cells from young mice. Additionally we found more of the protein misfolding indicator protein, GADD 153, in fibroblasts from old tendon. These results indicate that changes in tendon fibroblast function may well explain the age-related decline in tendon healing.
在衰老过程中，肌腱中胶原蛋白交联的增加和胶原蛋白总量的增多会导致其柔韧性以及损伤后愈合能力下降。成纤维细胞负责合成构成肌腱组织的大分子。随着年龄增长，成纤维细胞维持组织稳态的能力受损，这是许多肌肉骨骼系统与年龄相关的病理状况的潜在原因。这导致结缔组织愈合减缓。这些缺陷是由于结缔组织结构的变化还是肌腱成纤维细胞功能的变化尚不清楚。我们发现，与年轻小鼠的成纤维细胞相比，老年小鼠的肌腱成纤维细胞形态改变、功能水平降低，并且在蛋白质转运方面表现出变化。老年小鼠的成纤维细胞并非衰老细胞，它们是不同的表型。与年轻小鼠相同细胞相比，老年小鼠的跟腱成纤维细胞运动性和增殖能力较低，肌动蛋白细胞骨架组织紊乱，关键粘着斑蛋白定位不同。此外，我们在老年肌腱的成纤维细胞中发现了更多蛋白质错误折叠指示蛋白GADD 153。这些结果表明，肌腱成纤维细胞功能的变化很可能解释了与年龄相关的肌腱愈合能力下降。
