Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification.
Lymphatic Contribution to the Cellular Niche in Heterotopic Ossification.
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DOI：
10.1097/sla.0000000000001619
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发表时间：
2016-12
影响因子：
9
通讯作者：
Levi B
中科院分区：
文献类型：
--
作者：
Loder S;Agarwal S;Sorkin M;Breuler C;Li J;Peterson J;Gardenier J;Hsieh HH;Wang SC;Mehrara BJ;Levi B
本研究的目的是确定淋巴组织在异位骨化中的作用。异位骨化（HO）是严重创伤后软组织内异位骨的病理发展。支持HO的组织生态位的表征对于鉴定针对这种病症的疗法至关重要。淋巴管生成在创伤事件中上调，从而与HO的支持性小生境同时发生。我们假设淋巴组织在HO形成中起关键作用。对小鼠进行后肢跟腱横断和背部烧伤（烧伤/肌腱切断术）以诱导HO。切除肌腱切开部位同侧的腘淋巴结和腹股沟淋巴结。流式细胞术和免疫染色用于定量和定位淋巴内皮细胞。MicroCT用于定量HO。损伤后2周，与对侧基于LYVE 1+小管的完整肌腱相比，在肌腱横断部位观察到成熟淋巴组织的富集（10.9% v. 0.8%，p<0.05）。损伤后2周，切除腹股沟和腘淋巴结并引流腘淋巴管可显著降低成熟淋巴内皮的存在（10.9% v.3.3%，p<0.05）。骨软骨基质祖细胞（CD 105 +/AlphaV+/Tie 2 −/CD 45 −/CD 90 −/BP 1 −）在淋巴结切除后也显著减少（10.2% v. 0.5%，p<0.05）。观察到软组织中存在的原发HO体积显著减少（0.12 mm^3 v. 0.02 mm^3）。这些发现表明淋巴管与创伤后软组织内的新生骨形成密切相关，它们的存在可能有助于骨形成。
The objective of this study was to determine the contribution of lymphatic tissue to heterotopic ossification. Heterotopic ossification (HO) is the pathologic development of ectopic bone within soft tissues often following severe trauma. Characterization of the tissue niche supporting HO is critical to identifying therapies directed against this condition. Lymphangiogenesis is up-regulated during incidents of trauma, thereby co-incident with the niche supportive of HO. We hypothesized that lymphatic tissues play a critical role in HO formation. Mice underwent hindlimb Achilles’ tendon transection and dorsal burn injury(burn/tenotomy) to induce HO. The popliteal and inguinal lymph nodes were excised ipsilateral to the tenotomy site. Flow cytometry and immunostaining were used to quantify and localize lymphoendothelium. MicroCT was used to quantify HO. Enrichment of mature lymphatic tissues was noted 2 weeks after injury at the tendon transection sites when compared with the contralateral, intact tendon based on LYVE1+ tubules (10.9% v. 0.8%, p<0.05). Excision of the inguinal and popliteal nodes with draining popliteal lymphatic vessel significantly decreased the presence of mature lymphoendothelium 2 weeks after injury (10.9% v. 3.3%, p<0.05). Bone-cartilage-stromal progenitor cells (CD105+/AlphaV+/Tie2−/CD45−/CD90−/BP1−) were also significantly decreased after lymph node excision (10.2% v. 0.5%, p<0.05). A significant decrease was noted in the volume of de novo HO present within the soft tissues (0.12 mm^3 v. 0.02 mm^3). These findings suggest that lymphatic vessels are intimately linked with the formation de novo bone within soft tissues following trauma, and their presence may facilitate bone formation.