Basso Nick, Heersche Johan N M
Dental Research Institute, Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6.
Bone. 2006 Oct;39(4):807-14. doi: 10.1016/j.bone.2006.04.014. Epub 2006 Jun 12.
In rat bone, the absence of mechanical load results in a reduction in bone formation, inhibition of longitudinal growth, and a decrease in the number of osteoblasts and osteoprogenitors in cancellous bone. Unloading has also been linked to an increase in apoptosis of osteocytes and chondrocytes through production of nitric oxide (NO) and increased expression of NO synthases (NOS). Reloading results in recovery of bone volume within 14 days, although osteoblast and osteoclast numbers remain below control values, suggesting decreased bone turnover. This study was designed to evaluate the effects of hind limb unloading and subsequent reloading on apoptosis, NOS expression, and histomorphometric parameters in trabecular and cortical bone, articular cartilage, and growth plate cartilage of the proximal tibia of the hind limbs. Compared to ambulatory controls, 2 weeks of unloading resulted in a 66% increase in the percentage of apoptotic osteocytes in the trabecular metaphysis, a 14% increase in osteoclast number and a 48% decrease in bone volume. The percentage of eNOS- or iNOS-positive osteocytes was unchanged. Upon reloading, the percentage of apoptotic osteocytes and bone volume returned to baseline whereas the percentage of iNOS-positive osteocytes increased by 50% and osteoclast number decreased by 30% compared to ambulatory controls. More striking changes were observed in articular and growth plate cartilage. Unloading resulted in a 230% increase in apoptotic chondrocytes, a 400% increase in iNOS-positive chondrocytes, and a 17% reduction in width in articular cartilage. Reloading for 2 weeks resulted in partial recovery. Chondrocytes in the proliferative and hypertrophic zones of the growth plate responded similarly to those in the articular cartilage. In summary, we observed that 14 days of unloading increased apoptosis of osteocytes and chondrocytes. This was associated with an increase in the proportion of iNOS-positive chondrocytes whereas the proportion of iNOS-positive osteocytes remained unchanged. Reloading for 14 days restored osteocyte apoptosis to control levels but the percentage of iNOS- and eNOS-positive osteocytes increased in reloaded bone compared to controls. This was associated with a decrease in osteoclast number. In cartilage, reloading for 2 weeks did not result in a return to baseline in any of the parameters measured, suggesting that the effects of unloading on articular cartilage and the growth plate last longer than those in bone and may have prolonged effects on joint biomechanics and longitudinal bone growth.
在大鼠骨骼中，缺乏机械负荷会导致骨形成减少、纵向生长受到抑制，以及松质骨中骨细胞和成骨祖细胞数量减少。卸载还与骨细胞和软骨细胞凋亡增加有关，这是通过一氧化氮（NO）的产生以及一氧化氮合酶（NOS）表达增加介导的。再加载可在14天内使骨量恢复，尽管成骨细胞和破骨细胞数量仍低于对照值，这表明骨转换降低。本研究旨在评估后肢卸载及随后再加载对后肢胫骨近端小梁骨、皮质骨、关节软骨和生长板软骨中细胞凋亡、NOS表达及组织形态计量学参数的影响。与活动对照组相比，2周的卸载导致小梁干骺端凋亡骨细胞百分比增加66%，破骨细胞数量增加14%，骨量减少48%。内皮型一氧化氮合酶（eNOS）或诱导型一氧化氮合酶（iNOS）阳性骨细胞的百分比没有变化。再加载后，凋亡骨细胞百分比和骨量恢复到基线水平，而与活动对照组相比，iNOS阳性骨细胞百分比增加50%，破骨细胞数量减少30%。在关节软骨和生长板软骨中观察到更显著的变化。卸载导致凋亡软骨细胞增加230%，iNOS阳性软骨细胞增加400%，关节软骨宽度减少17%。再加载2周导致部分恢复。生长板增殖区和肥大区的软骨细胞与关节软骨中的软骨细胞反应相似。总之，我们观察到14天的卸载增加了骨细胞和软骨细胞的凋亡。这与iNOS阳性软骨细胞比例增加有关，而iNOS阳性骨细胞比例保持不变。再加载14天使骨细胞凋亡恢复到对照水平，但与对照相比，再加载骨中iNOS和eNOS阳性骨细胞的百分比增加。这与破骨细胞数量减少有关。在软骨中，再加载2周并未使所测任何参数恢复到基线水平，这表明卸载对关节软骨和生长板的影响持续时间长于对骨骼的影响，并且可能对关节生物力学和骨骼纵向生长产生长期影响。
