Department of Orthopaedic Surgery, University of California Davis Health, Sacramento, California, USA.
Physical & Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California, USA.
J Orthop Res. 2022 Apr;40(4):891-900. doi: 10.1002/jor.25119. Epub 2021 Jun 21.
We previously showed that femur fracture in mice caused a reduction in bone volume at distant skeletal sites within 2 weeks post-fracture. Osteocytes also have the ability to remodel their surrounding bone matrix through perilacunar/canalicular remodeling (PLR). If PLR is altered systemically following fracture, this could affect bone mechanical properties and increase fracture risk at all skeletal sites. In this study, we investigated whether lacunar-canalicular microstructure and the rate of PLR are altered in the contralateral limb following femoral fracture in mice. We hypothesized that femoral fracture would accelerate PLR by 2 weeks postfracture, followed by partial recovery by 4 weeks. We used histological evaluation and high-resolution microcomputed tomography to quantify the morphology of the lacunar-canalicular network at the contralateral tibia, and we used quantitative real-time polymerase chain reaction (RT-PCR) and RNA-seq to measure the expression of PLR-associated genes in the contralateral femur. We found that at both 2 and 4 weeks postfracture, canalicular width was significantly increased by 18.6% and 16.6%, respectively, in fractured mice relative to unfractured controls. At 3 days and 4 weeks post-fracture, we observed downregulation of PLR-associated genes; RNA-seq analysis at 3 days post-fracture showed a deceleration of bone formation and mineralization in the contralateral limb. These data demonstrate notable canalicular changes following fracture that could affect bone mechanical properties. These findings expand our understanding of systemic effects of fracture and how biological and structural changes at distant skeletal sites may contribute to increased fracture risk following an acute injury.
我们之前曾表明，小鼠股骨骨折后 2 周内，远处骨骼部位的骨量减少。骨细胞还具有通过骨陷窝/管腔重塑（PLR）重塑周围骨基质的能力。如果骨折后系统性地改变 PLR，这可能会影响骨力学性能，并增加所有骨骼部位的骨折风险。在这项研究中，我们研究了在小鼠股骨骨折后，对侧肢体的陷窝/管腔微结构和 PLR 速率是否发生变化。我们假设股骨骨折会在骨折后 2 周内加速 PLR，然后在 4 周时部分恢复。我们使用组织学评估和高分辨率微计算机断层扫描来定量对侧胫骨陷窝/管腔网络的形态，并使用定量实时聚合酶链反应（RT-PCR）和 RNA 测序来测量对侧股骨中与 PLR 相关的基因的表达。我们发现，在骨折后 2 周和 4 周时，骨折小鼠的管腔宽度分别显著增加了 18.6%和 16.6%。在骨折后 3 天和 4 周时，我们观察到与 PLR 相关的基因下调；骨折后 3 天的 RNA 测序分析表明，对侧肢体的骨形成和矿化减速。这些数据表明骨折后出现明显的管腔变化，这可能会影响骨力学性能。这些发现扩展了我们对骨折全身影响的理解，以及远处骨骼部位的生物学和结构变化如何可能导致急性损伤后骨折风险增加。
