Heterotopic ossification (HO) is the process by which ectopic bone forms at an extraskeletal site. Inflammatory conditions induce plasminogen activator inhibitor 1 (PAI-1), an inhibitor of fibrinolysis, which regulates osteogenesis. In the present study, we investigated the roles of PAI-1 in the pathophysiology of HO induced by trauma/burn treatment using PAI-1-deficient mice. PAI-1 deficiency significantly promoted HO and increased the number of alkaline phosphatase (ALP)-positive cells in Achilles tendons after trauma/burn treatment. The mRNA levels of inflammation markers were elevated in Achilles tendons of both wild-type and PAI-1-deficient mice after trauma/burn treatment and PAI-1 mRNA levels were elevated in Achilles tendons of wild-type mice. PAI-1 deficiency significantly up-regulated the expression of Runx2, Osterix, and type 1 collagen in Achilles tendons 9 weeks after trauma/burn treatment in mice. In in vitro experiments, PAI-1 deficiency significantly increased ALP activity and mineralization in mouse osteoblasts. Moreover, PAI-1 deficiency significantly increased ALP activity and up-regulated osteocalcin expression during osteoblastic differentiation from mouse adipose-tissue-derived stem cells, but suppressed the chondrogenic differentiation of these cells. In conclusion, the present study showed that PAI-1 deficiency promoted HO in Achilles tendons after trauma/burn treatment partly by enhancing osteoblast differentiation and ALP activity in mice. Endogenous PAI-1 may play protective roles against HO after injury and inflammation.

异位骨化（HO）是在骨骼外部位形成异位骨的过程。炎症条件会诱导纤溶酶原激活剂抑制剂 1 (PAI-1)，这是一种纤维蛋白溶解抑制剂，可调节骨生成。在本研究中，我们使用 PAI-1 缺陷小鼠研究了 PAI-1 在创伤/烧伤治疗引起的 HO 病理生理学中的作用。PAI-1 缺乏显着促进创伤/烧伤治疗后跟腱中的 HO 并增加碱性磷酸酶 (ALP) 阳性细胞的数量。创伤/烧伤治疗后，野生型和 PAI-1 缺陷小鼠的跟腱中炎症标志物的 mRNA 水平均升高，并且野生型小鼠的跟腱中 PAI-1 mRNA 水平升高。在小鼠创伤/烧伤治疗后 9 周，PAI-1 缺陷显着上调跟腱中 Runx2、Osterix 和 1 型胶原的表达。在体外实验中，PAI-1 缺乏显着增加小鼠成骨细胞的 ALP 活性和矿化作用。此外，PAI-1缺陷显着增加了小鼠脂肪组织干细胞向成骨细胞分化过程中的ALP活性并上调骨钙蛋白表达，但抑制了这些细胞的软骨形成分化。总之，本研究表明，PAI-1 缺乏部分通过增强小鼠成骨细胞分化和 ALP 活性来促进创伤/烧伤治疗后跟腱中的 HO。内源性 PAI-1 可能对损伤和炎症后的 H2O2 发挥保护作用。