Liu Daquan, Li Xinle, Li Jie, Yang Jing, Yokota Hiroki, Zhang Ping
Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China; Department of Pharmacology, Institute of Acute Abdominal Diseases, Tianjin Nankai Hospital, Tianjin 300100, China.
Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
Bone. 2015 Dec;81:620-631. doi: 10.1016/j.bone.2015.09.012. Epub 2015 Sep 28.
Osteonecrosis of the femoral head is a serious orthopedic problem. Moderate loads with knee loading promote bone formation, but their effects on osteonecrosis have not been investigated. Using a rat model, we examined a hypothesis that knee loading enhances vessel remodeling and bone healing through the modulation of the fate of bone marrow-derived cells. In this study, osteonecrosis was induced by transecting the ligamentum teres followed by a tight ligature around the femoral neck. For knee loading, 5 N loads were laterally applied to the knee at 15 Hz for 5 min/day for 5 weeks. Changes in bone mineral density (BMD) and bone mineral content (BMC) of the femur were measured by pDEXA, and ink infusion was performed to evaluate vessel remodeling. Femoral heads were harvested for histomorphometry, and bone marrow-derived cells were isolated to examine osteoclast development and osteoblast differentiation. The results showed that osteonecrosis significantly induced bone loss, and knee loading stimulated both vessel remodeling and bone healing. The osteonecrosis group exhibited the lowest trabecular BV/TV (p b 0.001) in the femoral head, and lowest femoral BMD and BMC (both p b 0.01). However, knee loading increased trabecular BV/TV (p b 0.05) as well as BMD (pb 0.05) and BMC (p b 0.01). Osteonecrosis decreased the vessel volume (pb 0.001), vessel number (pb 0.001) and VEGF expression (p b 0.01), and knee loading increased them (pb 0.001, pb 0.001 and p b 0.01). Osteonecrosis activated osteoclast development, and knee loading reduced its formation, migration, adhesion and the level of “pit” formation (pb 0.001, pb 0.01, pb 0.001 and pb 0.001). Furthermore, knee loading significantly increased osteoblast differentiation and CFU-F (both p b 0.001). A significantly positive correlation was observed between vessel remodeling and bone healing (both p b 0.01). These results indicate that knee loading could be effective in repair osteonecrosis of the femoral head in a rat model. This effect might be attributed to promoting vessel remodeling, suppressing osteoclast development, and increasing osteoblast and fibroblast differentiation. In summary, the current study suggests that knee loading might potentially be employed as a non-invasive therapy for osteonecrosis of the femoral head.
股骨头坏死是一个严重的骨科问题。膝关节负荷的适度负重可促进骨形成，但其对坏死的影响尚未得到研究。我们使用大鼠模型检验了一个假设，即膝关节负荷通过调节骨髓来源细胞的命运来增强血管重塑和骨愈合。在本研究中，通过切断圆韧带并在股骨颈周围进行紧密结扎来诱导坏死。对于膝关节负荷，以15Hz的频率向膝关节外侧施加5N的负荷，每天5分钟，持续5周。通过pDEXA测量股骨的骨密度（BMD）和骨矿物质含量（BMC）的变化，并进行墨水灌注以评估血管重塑。采集股骨头进行组织形态计量学分析，并分离骨髓来源细胞以检查破骨细胞发育和成骨细胞分化。结果表明，坏死显著导致骨质流失，而膝关节负荷刺激了血管重塑和骨愈合。坏死组在股骨头中表现出最低的小梁骨体积分数（p<0.001），以及最低的股骨BMD和BMC（均为p<0.01）。然而，膝关节负荷增加了小梁骨体积分数（p<0.05）以及BMD（p<0.05）和BMC（p<0.01）。坏死降低了血管体积（p<0.001）、血管数量（p<0.001）和VEGF表达（p<0.01），而膝关节负荷增加了它们（p<0.001、p<0.001和p<0.01）。坏死激活了破骨细胞发育，而膝关节负荷减少了其形成、迁移、黏附以及“凹陷”形成水平（p<0.001、p<0.01、p<0.001和p<0.001）。此外，膝关节负荷显著增加了成骨细胞分化和集落形成单位 - 成纤维细胞（均为p<0.001）。在血管重塑和骨愈合之间观察到显著的正相关（均为p<0.01）。这些结果表明，在大鼠模型中膝关节负荷可能对修复股骨头坏死有效。这种作用可能归因于促进血管重塑、抑制破骨细胞发育以及增加成骨细胞和成纤维细胞分化。总之，当前研究表明膝关节负荷可能潜在地用作股骨头坏死的非侵入性治疗方法。
