Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis.
Low level laser therapy promotes bone regeneration by coupling angiogenesis and osteogenesis.
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低强度激光治疗通过耦合血管生成和成骨来促进骨再生
DOI：
10.1186/s13287-021-02493-5
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发表时间：
2021-08-03
影响因子：
7.5
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Bai J;Li L;Kou N;Bai Y;Zhang Y;Lu Y;Gao L;Wang F
研究背景骨组织工程是一个新概念，为大骨缺损的修复带来了希望，但大骨缺损仍然是临床的一大挑战。血管化骨的形成是骨组织工程的关键。称为 H 型的特殊血管的生长与骨形成相关。体内和体外研究表明，低强度激光疗法（LLLT）通过增加活性氧（ROS）来促进血管生成、骨折愈合和干细胞的成骨分化。然而，LLLT是否能够耦合血管生成和成骨，以及骨形成过程中的潜在机制仍不清楚。方法将小鼠骨髓间充质干细胞（BMSCs）联合双相磷酸钙（BCP）移植物植入C57BL/6小鼠体内，评价LLLT对体内特化血管亚型和骨再生的影响。此外，人骨髓间充质干细胞和人脐静脉内皮细胞（HUVEC）在体外共培养。评估LLLT对细胞增殖、血管生成和成骨的影响。结果LLLT促进了植入小鼠的mBMSC/BCP移植物中血管、胶原纤维和骨组织的形成，并增加了表达CD31hiEMCNhi的H型血管。 LLLT 显着增加体内移植物和体外共培养的 BMSC/HUVEC 的成骨和血管生成以及相关基因表达（HIF-1α、VEGF、TGF-β）。 H2O2 或维生素 C 诱导的 ROS 的增加或减少分别导致共培养系统中 HIF-1α 的增加或减少，以及随后 VEGF 和 TGF-β 的增加或减少。当DMBPA抑制HIF-1α时，LLLT在共培养系统中诱导的ROS积累显着减少，随后VEGF和TGF-β的表达降低。结论LLLT通过耦合血管生成和成骨来增强血管化骨再生。 ROS/HIF-1α 对于 LLLT 的这些作用是必要的。 LLLT 触发 ROS 依赖性 HIF-1α、VEGF 和 TGF-β 的增加，并导致随后 H 型血管的形成和间充质干细胞的成骨分化。由于 ROS 也是 HIF-1α 的靶标，因此 ROS 和 HIF-1α 之间可能存在正反馈环，这通过 LLLT 介导的 ROS 增加进一步放大了 HIF-1α 的诱导。这项研究为骨组织工程中 LLLT 对血管化和骨再生的影响提供了新的见解。
BackgroundBone tissue engineering is a new concept bringing hope for the repair of large bone defects, which remains a major clinical challenge. The formation of vascularized bone is key for bone tissue engineering. Growth of specialized blood vessels termed type H is associated with bone formation. In vivo and in vitro studies have shown that low level laser therapy (LLLT) promotes angiogenesis, fracture healing, and osteogenic differentiation of stem cells by increasing reactive oxygen species (ROS). However, whether LLLT can couple angiogenesis and osteogenesis, and the underlying mechanisms during bone formation, remains largely unknown.MethodsMouse bone marrow mesenchymal stem cells (BMSCs) combined with biphasic calcium phosphate (BCP) grafts were implanted into C57BL/6 mice to evaluate the effects of LLLT on the specialized vessel subtypes and bone regeneration in vivo. Furthermore, human BMSCs and human umbilical vein endothelial cells (HUVECs) were co-cultured in vitro. The effects of LLLT on cell proliferation, angiogenesis, and osteogenesis were assessed.ResultsLLLT promoted the formation of blood vessels, collagen fibers, and bone tissue and also increased CD31hiEMCNhi-expressing type H vessels in mBMSC/BCP grafts implanted in mice. LLLT significantly increased both osteogenesis and angiogenesis, as well as related gene expression (HIF-1α, VEGF, TGF-β) of grafts in vivo and of co-cultured BMSCs/HUVECs in vitro. An increase or decrease of ROS induced by H2O2or Vitamin C, respectively, resulted in an increase or decrease of HIF-1α, and a subsequent increase and decrease of VEGF and TGF-β in the co-culture system. The ROS accumulation induced by LLLT in the co-culture system was significantly decreased when HIF-1α was inhibited with DMBPA and was followed by decreased expression of VEGF and TGF-β.ConclusionsLLLT enhanced vascularized bone regeneration by coupling angiogenesis and osteogenesis. ROS/HIF-1α was necessary for these effects of LLLT. LLLT triggered a ROS-dependent increase of HIF-1α, VEGF, and TGF-β and resulted in subsequent formation of type H vessels and osteogenic differentiation of mesenchymal stem cells. As ROS also was a target of HIF-1α, there may be a positive feedback loop between ROS and HIF-1α, which further amplified HIF-1α induction via the LLLT-mediated ROS increase. This study provided new insight into the effects of LLLT on vascularization and bone regeneration in bone tissue engineering.
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影响因子：
2.4
作者：
Chen, Chung-Huang;Hung, Huey-Shan;Hsu, Shan-Hui
通讯作者：
Hsu, Shan-Hui
影响因子：
29
作者：
Codo, Ana Campos;Davanzo, Gustavo Gastao;Moraes-Vieira, Pedro M.
通讯作者：
Moraes-Vieira, Pedro M.
影响因子：
--
作者：
Carrinho, Patricia M.;Muniz Renno, Ana Claudia;Vidal, Benedito Campos
通讯作者：
Vidal, Benedito Campos
影响因子：
64.8
作者：
Kusumbe AP;Ramasamy SK;Adams RH
通讯作者：
Adams RH
影响因子：
56.9
作者：
LANGER, R;VACANTI, JP
通讯作者：
VACANTI, JP