Soft tissue injury in the limbs increased regional bone turnover
Soft tissue injury in the limbs increased regional bone turnover
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DOI：
10.1016/j.injury.2020.12.019
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发表时间：
2021-05-26
影响因子：
2.5
通讯作者：
Yamashita，Toshihiko
中科院分区：
文献类型：
--
作者：
Hayakawa，Hikaru;Hanaka，Megumi;Yamashita，Toshihiko
研究背景创伤、手术等骨骼组织损伤后的病理状态常伴有局部的病理改变，而这些病理改变主要是由于损伤后肢体不能活动所致。然而，与损伤相关的局部神经病变进展的机制仍不清楚。以往的研究报道，与组织损伤相关的病理生理条件包括酸性微环境的形成和ATP水平的升高。此外，我们之前证明了微环境的这些变化通过激活骨细胞中表达的TRPV 1，ASIC和P2 X诱导高骨转换状态。因此，我们假设，组织损伤可以提高高骨转换状态，由于这些病理生理变化的软组织在受伤的肢体。本研究的目的是检查是否与皮肤切口在肢体软组织损伤影响区域骨turning. MethodsEight周龄的男性C57 BL/6 J小鼠进行了软组织损伤与皮肤切口在右股骨皮肤。在14天后的切口，成骨细胞和破骨细胞分化调节因子和ATP的表达的变化进行了评估，与未受伤的小鼠相比。疼痛样行为和表达的分化调节剂与和没有治疗的双膦酸盐和Cox 2抑制剂进行了评估，在受伤limb.ResultsConsistent与伤口愈合过程中，表达水平的Osterix，骨钙素和RANKL在股骨的切割肢体显着增加了7天，术后14 d，再降至对照组水平。TRAP 5 b和ATP的水平最初显著增加，然后在第14天下降到与损伤前相同的水平。双膦酸盐显着改善疼痛样行为与抑制成骨细胞和破骨细胞分化regulator.ConclusionWe认为，在软组织中的病理生理变化导致皮肤切口可能与成骨细胞和破骨细胞分化调节剂的诱导。
BackgroundPathological conditions after skeletal tissue injury such as trauma and surgical intervention are often accompanied with regional osteoporotic changes, which are recognized to be mainly caused by limb immobility after injury. However, the mechanisms for the progression of regional osteoporotic changes related to the injury remains unknown. Previous studies reported that the pathophysiological conditions related to tissue injury include the acidic micro-environment formation and increased ATP levels. In addition, we previously demonstrated that those changes in the micro-environment induced a high bone turnover state through the activation of TRPV1, ASICs and P2X expressed in bone cells. We, therefore, hypothesized that tissue injury could enhance a high bone turnover state due to those pathophysiological changes in soft tissue in the injured limb. The aim of this study was to examine whether soft tissue injury associated with cutaneous incisions in a limb affects regional bone turnover.MethodsEight-week-old male C57BL/6 J mice underwent soft tissue injury associated with cutaneous incisions in the right femoral skin. During the 14 days after the incision, changes in the expression of osteoblast and osteoclast differentiation regulators and ATP were evaluated in comparison with those in uninjured mice. The pain-like behaviors and the expression of those differentiation regulators with and without treatment with bisphosphonate and Cox2 inhibitor were assessed in the injured limb.ResultsConsistent with the wound healing process, the expression levels of Osterix, osteocalcin and RANKL in the femur of the incised limb were significantly increased up to 7 days, and then decreased to the same level as those in the control limbs by 14 days after the incisions. The levels of TRAP 5b and ATP were initially significantly increased, and then decreased to the same level as before injury by day 14. Bisphosphonate significantly improved the pain-like behaviors in the injured limb associated with the inhibition of osteoblast and osteoclast differentiation regulators.ConclusionWe believe that the pathophysiological changes in soft tissue resulting from cutaneous incisions could be related to the induction of osteoblast and osteoclast differentiation regulators.