Jiang S-D, Jiang L-S, Dai L-Y
Department of Orthopaedic Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, 1665 Kongjiang Road, Shanghai, China.
Osteoporos Int. 2007 Mar;18(3):339-49. doi: 10.1007/s00198-006-0229-4. Epub 2006 Oct 12.
Spinal cord injury (SCI) causes a significant amount of bone loss in the sublesional area in animals and humans, and this type of bone loss is different from other forms of osteoporosis such as disuse osteoporosis and postmenopausal osteoporosis. However, no data is available on the cellular and molecular changes of osteoblastogenesis and osteoclastogenesis during SCI-induced bone loss.
SCI and SHAM rats were used in this study to investigate osteoblastogenesis and osteoclastogenesis in bone-marrow culture. We also measured bone mass and bone histomorphometry, as well as the expression of alkaline phosphatase (ALP), core binding factor alpha1 (Cbfa-1), osterix, receptor activator of NF-kappaB ligand (RANKL) and osteoprotegerin (OPG) in osteoblast-like cells in bone-marrow culture obtained from SCI and SHAM rats.
Bone mineral density (BMD) measurement showed serious bone loss in the tibial ephiphyses and metaphyses of SCI rats compared with SHAM rats. In addition, bone histomorphometry analysis of the tibial metaphyses of SCI rats demonstrated that bone microarchitecture in SCI rats deteriorated further than in SHAM rats, and increased eroded surfaces and bone formation rates were observed in SCI rats. The number of osteoclasts that developed from bone marrow of SCI rats at equal density was significantly increased compared with SHAM rats, and the area of the resorption pits formed in the bone marrow culture from SCI rats was significantly greater than SHAM rats, whereas the number of CFU-F and CFU-OB was similar in both groups. RANKL mRNA and protein levels in osteoblast-like cells in culture obtained from SCI rats were significantly higher than those from the SHAM rats, whereas OPG levels decreased slightly. The ratios of RANKL to OPG expression in SCI rats were significantly higher than those in SHAM rats. However, osteogenic gene profiling of Cbfa-1, ALP and osterix in SCI rats remained similar with SHAM rats.
These changes favor increased osteoclast activity over osteoblast activity, and may explain, in part, the imbalance in bone formation and resorption following SCI.
脊髓损伤（SCI）在动物和人类的损伤节段以下区域会导致大量骨质流失，且这种骨质流失不同于废用性骨质疏松和绝经后骨质疏松等其他形式的骨质疏松。然而，关于SCI诱导的骨质流失过程中成骨细胞生成和破骨细胞生成的细胞及分子变化尚无相关数据。
本研究使用SCI大鼠和假手术（SHAM）大鼠来研究骨髓培养中的成骨细胞生成和破骨细胞生成。我们还测量了骨量和骨组织形态计量学指标，以及从SCI大鼠和SHAM大鼠获得的骨髓培养中成骨样细胞中碱性磷酸酶（ALP）、核心结合因子α1（Cbfa-1）、osterix、核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）的表达。
骨密度（BMD）测量显示，与SHAM大鼠相比，SCI大鼠胫骨骨骺和干骺端存在严重骨质流失。此外，对SCI大鼠胫骨干骺端的骨组织形态计量学分析表明，SCI大鼠的骨微结构比SHAM大鼠进一步恶化，且SCI大鼠的侵蚀表面和骨形成率增加。与SHAM大鼠相比，同等密度下由SCI大鼠骨髓发育而来的破骨细胞数量显著增加，且SCI大鼠骨髓培养中形成的吸收陷窝面积显著大于SHAM大鼠，而两组的集落形成单位-成纤维细胞（CFU-F）和集落形成单位-成骨细胞（CFU-OB）数量相似。从SCI大鼠获得的培养成骨样细胞中RANKL的mRNA和蛋白水平显著高于SHAM大鼠，而OPG水平略有下降。SCI大鼠中RANKL与OPG表达的比值显著高于SHAM大鼠。然而，SCI大鼠中Cbfa-1、ALP和osterix的成骨基因谱与SHAM大鼠相似。
这些变化有利于破骨细胞活性高于成骨细胞活性，这可能部分解释了SCI后骨形成与吸收的失衡。
