Department of Sports Medicine Center, Southwest Hospital, Army Medical University, Chongqing, China.
Department of Blood Transfusion, Xinqiao Hospital, Army Medical University, Chongqing, China.
FASEB J. 2022 Aug;36(8):e22433. doi: 10.1096/fj.202200213R.
Studies have shown that the stem cell microenvironment is a key factor for stem cell maintenance or differentiation. In this study, we compared the expression of 23 cytokines such as IL-6, IL-10, and TNFα between young and aged rats during patellar tendon repair by cytokine microarray, and found that significant difference between IL-10, G-CSF, and VEGF at 3, 7, or 14 days post-operatively. The effects of these factors on adipogenic differentiation of TPSCs were examined through western blot and oil red O experiments. It was shown that VEGF had an inhibitive effect on the adipogenic differentiation of TPSCs. SPP-1 was figured out as our target by RNA sequencing and confirmed by western blot in vitro. Further in vivo studies showed that adipocyte accumulation was also decreased in the tendons of aged rats after injection of VEGF and the histological score and biomechanical property were also improved via targeting SPP-1. Furthermore, histochemical results showed that vascularization of the injury sites was significantly elevated. In conclusion, VEGF not only plays an important role in decreasing adipocyte accumulation but also improves vascularization of the tendon during aged tendon healing. We believe active regulation of VEGF may improve the treatment of age-related tendon diseases and tendon injuries.
研究表明，干细胞微环境是维持或分化干细胞的关键因素。在这项研究中，我们通过细胞因子微阵列比较了年轻和老年大鼠在髌腱修复过程中 23 种细胞因子（如 IL-6、IL-10 和 TNFα）的表达，发现术后 3、7 或 14 天，IL-10、G-CSF 和 VEGF 之间存在显著差异。通过 Western blot 和油红 O 实验研究了这些因子对 TPSC 成脂分化的影响。结果表明，VEGF 对 TPSC 的成脂分化有抑制作用。通过 RNA 测序确定 SPP-1 是我们的靶标，并通过体外 Western blot 进行了验证。进一步的体内研究表明，在注射 VEGF 后，老年大鼠肌腱中的脂肪细胞积累也减少，通过靶向 SPP-1，组织学评分和生物力学性能也得到改善。此外，组织化学结果表明，损伤部位的血管化明显增加。总之，VEGF 不仅在减少脂肪细胞积累方面发挥重要作用，而且在老年肌腱愈合过程中还改善了肌腱的血管化。我们相信，VEGF 的积极调节可能会改善与年龄相关的肌腱疾病和肌腱损伤的治疗效果。
