To investigate the osteoinductive mechanism triggered by hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) biomaterials in mice which keep exercising. Methods: The HA/β-TCP biomaterials were implanted in the muscle of bilateral thighs (non-osseous sites) of eighty Balb/C mice. All animals were then randomly divided into 4 groups (n = 20). In group 1 (negative control group), the mice were fed routinely. In group 2 (running group), all mice were put on a treadmill which was set to a 60-degree incline. The mice ran 20 min thrice each day. A 5-minute break was included in the routine from day three onwards. In group 3 (weight-bearing group), all mice underwent weight-bearing running. The mice in this group performed the same routine as group 2 while carrying 5 g rubber weights. In group 4 (positive control group), dexamethasone was injected in the implanted sites of the biomaterials from the day of the operation. All mice were injected once per week and received a total of 8 injections. One and eight weeks after surgery, the blood serum was collected to detect inflammatory and immunological factors by ELISA. In addition to this, biomaterial specimens were obtained to observe inflammatory and osteogenic levels via histological staining and to facilitate analysis of the osteogenic mechanism by Western Blot. Results: The inflammation indexes caused by surgery were alleviated through running or weight-bearing running: The tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly reduced in groups 2 and 3 at week 8. Exercise also enhanced the secretion of interferon-γ (IFN-γ) in mice; this can strengthen their immunity. The new bone tissues were observed in all groups; however, the area percentage of new bone tissues and the number of osteoblasts were highest in the weight-bearing group. Furthermore, the key proteins of wingless/integrated (Wnt) signaling pathway, Wnt1, Wnt3a, and β-catenin, were up-regulated during osteoinduction. This up-regulation activated runt-related transcription factor-2 (Runx2), increased the expression of osteopontin (OPN) and osteocalcin (OCN). Conclusion: Weight-bearing exercise can promote the bone and bone marrow formation through the Wnt signaling pathway: Observations documented here suggest that the proper exercise is beneficial to the recovery of bone damage.

中文翻译：

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运动通过Wnt信号通路促进HA /β-TCP生物材料的成骨诱导

研究由羟基磷灰石/β-磷酸三钙（HA /β-TCP）生物材料触发的持续运动小鼠的骨诱导机制。方法：将HA /β-TCP生物材料植入到80只Balb / C小鼠的双腿大腿（非骨性部位）的肌肉中。然后将所有动物随机分为4组（n = 20）。在第1组（阴性对照组）中，常规喂养小鼠。在第2组（跑步组）中，将所有小鼠放在设置为60度倾斜的跑步机上。小鼠每天跑20分钟三次。从第三天开始，例行休息时间为5分钟。在第3组（负重组）中，所有小鼠都进行负重跑步。该组小鼠携带5 g橡胶砝码，执行与第2组相同的程序。在第4组（阳性对照组），自手术当天起，将地塞米松注射入生物材料的植入部位。所有小鼠每周注射一次，共接受8次注射。手术后一和八周，收集血清以通过ELISA检测炎性和免疫学因素。除此之外，还获得了生物材料标本，以通过组织学染色观察炎症和成骨水平，并通过Western Blot促进对成骨机制的分析。结果：通过跑步或负重跑步减轻了由手术引起的炎症指标：第8周第2和第3组的肿瘤坏死因子-α（TNF-α）和白介素-6（IL-6）水平明显降低。运动还增强了小鼠中干扰素-γ（IFN-γ）的分泌；这样可以增强他们的免疫力。在所有组中均观察到了新的骨组织。然而，在负重组中新骨组织的面积百分比和成骨细胞的数量最高。此外，在骨诱导过程中，无翅/整合（Wnt）信号通路的关键蛋白Wnt1，Wnt3a和β-catenin均被上调。这种上调激活了矮子相关转录因子2（Runx2），增加了骨桥蛋白（OPN）和骨钙素（OCN）的表达。结论：负重运动可以通过Wnt信号通路促进骨骼和骨髓的形成：此处记录的观察结果表明，适当的运动有益于骨骼损伤的恢复。