Baltimore VA Medical Center, VA Maryland Healthcare System, Baltimore, Maryland, USA.
Department of Orthopaedic Surgery, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Orthop Res. 2023 Sep;41(9):1882-1889. doi: 10.1002/jor.25552. Epub 2023 Mar 22.
The purpose of this study was to track platelet-derived growth factor receptor-β (Pdgfr-β) lineage cells at the site of Achilles tendon injury over time. Pdgfr-β-CreER :Ai9 mice were generated to track Pdgfr-β lineage cells in adult mice. A surgical Achilles transection injury model was employed to examine the presence of Pdgfr-β lineage cells in the healing tendon over time, with five mice per time point at 3, 7, 14, 28, and 56 days postoperatively. Histology and immunohistochemistry for tdTomato (Pdgfr-β lineage cells), PCNA (proliferating cell nuclear antigen, cell proliferation), and α-SMA (α-smooth muscle actin, myofibroblasts) were performed. The percentage of cells at the healing tendon site staining positive for tdTomato and PCNA were quantified. Over 75% of cells at the injury site were Pdgfr-β lineage cells at Days 3, 7, and 14, and this percentage decreased significantly by Days 28 and 56 postinjury. Cell proliferation at the injury site peaked on Day 7 and decreased thereafter. Immunohistochemistry for α-SMA demonstrated minimal colocalization of myofibroblasts with Pdgfr-β lineage cells. This study demonstrates that in a mouse model of Achilles tendon injury, Pdgfr-β lineage cells' presence at the injury site is transient. Thus, we conclude that they are unlikely to be the cells that differentiate into myofibroblasts and directly contribute to tendon fibrous scar formation. Clinical Significance: This study provides some insight into the presence of Pdgfr-β lineage cells (including pericytes) following Achilles injury, furthering our understanding of tendon healing.
这项研究的目的是追踪血小板衍生生长因子受体-β（Pdgfr-β）谱系细胞在跟腱损伤部位随时间的变化。生成了 Pdgfr-β-CreER：Ai9 小鼠，以追踪成年小鼠中 Pdgfr-β 谱系细胞。采用手术跟腱横断损伤模型，随时间推移，在术后第 3、7、14、28 和 56 天，在愈合的跟腱中检查 Pdgfr-β 谱系细胞的存在情况，每个时间点有 5 只小鼠。进行组织学和免疫组织化学染色，检测 tdTomato（Pdgfr-β 谱系细胞）、PCNA（增殖细胞核抗原，细胞增殖）和 α-SMA（α-平滑肌肌动蛋白，肌成纤维细胞）。对 tdTomato 和 PCNA 染色阳性的细胞在愈合的跟腱部位的百分比进行定量。损伤部位有超过 75%的细胞是 Pdgfr-β 谱系细胞，在第 3、7 和 14 天，这一比例在损伤后第 28 和 56 天显著下降。损伤部位的细胞增殖在第 7 天达到峰值，此后逐渐下降。α-SMA 的免疫组织化学染色显示肌成纤维细胞与 Pdgfr-β 谱系细胞的共定位很少。这项研究表明，在小鼠跟腱损伤模型中，损伤部位 Pdgfr-β 谱系细胞的存在是短暂的。因此，我们得出结论，它们不太可能是分化为肌成纤维细胞并直接有助于肌腱纤维瘢痕形成的细胞。临床意义：这项研究为我们进一步了解跟腱愈合时 Pdgfr-β 谱系细胞（包括周细胞）的存在提供了一些见解。
