Uusitalo H, Rantakokko J, Vuorio E, Aro H T
Skeletal Research Program, Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
Bone. 2005 Jan;36(1):142-9. doi: 10.1016/j.bone.2004.09.010.
The present study was carried out to determine whether immobilization-induced (Im) osteopenic bone possesses the same reparative capacity as normal healthy bone. Furthermore, the effects of mechanical loading versus immobilization on bone defect healing were studied. Three-week cast-immobilization was used to induce local osteopenia in mice. A standardized metaphyseal bone defect of the distal femur was created unilaterally both in immobilization-induced (Im) osteopenic mice and in nonimmobilized (Mo) age-matched control animals. After creation of the bone defect, the animals in both groups were further divided into two groups: 3-week cast-immobilization (Im-Im and Mo-Im) groups, and unrestricted weight-bearing (Im-Mo and Mo-Mo) groups. The healing process was followed up to 3 weeks using RNA analysis, histomorphometry, biomechanical testing, and pQCT measurements. At 3 weeks of healing without immobilization, bone mineral density (BMD), as well as bone bending stiffness and strength were higher in normal (Mo-Mo) than in osteopenic (Im-Mo) bone. Although the levels of mRNAs characteristic to chondrocytes (Sox9 and type II collagen), hypertrophic chondrocytes (Type X collagen), osteoblasts (type I collagen and osteocalcin), and osteoclasts (cathepsin K) during the bone defect healing exhibited similarities in their expression profiles, mechanical loading conditions also caused characteristic differences. Mechanical loading during healing (Mo-Mo group) induced stronger expression of cartilage- and bone-specific genes and resulted in higher BMD than that seen in the cast-immobilized group (Mo-Im). In biomechanical analysis, increased bending stiffness and strength were also observed in animals that were allowed weight-bearing during healing. Thus, our study shows that bone healing follows the same molecular pathway both in osteopenic and normal bones and presents evidence for reduced or delayed regeneration of noncritical size defects in immobilization-induced osteopenic bone.
本研究旨在确定固定诱导的（Im）骨质减少性骨是否具有与正常健康骨相同的修复能力。此外，还研究了机械负荷与固定对骨缺损愈合的影响。采用为期三周的石膏固定来诱导小鼠局部骨质减少。在固定诱导的（Im）骨质减少小鼠和未固定的（Mo）年龄匹配对照动物中，单侧创建标准化的股骨远端干骺端骨缺损。创建骨缺损后，两组动物进一步分为两组：为期三周的石膏固定组（Im-Im和Mo-Im）和无限制负重组（Im-Mo和Mo-Mo）。使用RNA分析、组织形态计量学、生物力学测试和外周定量计算机断层扫描（pQCT）测量对愈合过程进行了长达3周的随访。在无固定愈合3周时，正常（Mo-Mo）骨的骨矿物质密度（BMD）以及骨弯曲刚度和强度均高于骨质减少（Im-Mo）骨。尽管在骨缺损愈合过程中，软骨细胞（Sox9和II型胶原）、肥大软骨细胞（X型胶原）、成骨细胞（I型胶原和骨钙素）和破骨细胞（组织蛋白酶K）特征性的mRNA水平在表达谱上表现出相似性，但机械负荷条件也导致了特征性差异。愈合过程中的机械负荷（Mo-Mo组）诱导软骨和骨特异性基因更强的表达，并导致比石膏固定组（Mo-Im）更高的BMD。在生物力学分析中，在愈合过程中允许负重的动物中也观察到弯曲刚度和强度增加。因此，我们的研究表明，骨愈合在骨质减少性骨和正常骨中遵循相同的分子途径，并为固定诱导的骨质减少性骨中非临界尺寸缺损的再生减少或延迟提供了证据。
