Basso N, Bellows C G, Heersche J N M
Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada M5G 1G6.
Bone. 2005 Jan;36(1):173-83. doi: 10.1016/j.bone.2004.09.016. Epub 2004 Nov 23.
Experiments with rats flown in space or hind limb unloaded (HU) indicate that bone loss in both conditions is associated with a decrease in bone volume and osteoblast surface in cancellous and cortical bone. We hypothesize that the decrease in osteoblastic bone formation and osteoblast surface is related to a decrease in the number of osteoprogenitors and/or decreased proliferation of their progeny. We tested this hypothesis by evaluating the effect of 14 days of HU on the number of osteoprogenitors (osteoblast colony forming units; CFU-O), fibroblastic colony forming units (CFU-F), and alkaline phosphatase-positive CFU (CFU-AP) in cell populations derived from the proximal femur (unloaded) and the proximal humerus (normally loaded) in 6-week-old and 6-month-old rats. To confirm the effect of unloading on bone volume and structure, static histomorphometric parameters were measured in the proximal tibial metaphysis. Effects of HU on proliferation of osteoprogenitors were evaluated by measuring the size of CFU-O. HU did not affect the total number of progenitors (CFU-F) in young or adult rats in any of the cell populations. In femoral populations of young rats, HU decreased CFU-O by 71.0% and mean colony size was reduced by 20%. HU decreased CFU-AP by 31.3%. As expected, no changes in CFU-O or CFU-AP were seen in cell populations from the humerus. In femoral cell populations of adult rats, HU decreased CFU-O and CFU-AP by 16.6% and 36.6%, respectively. Again, no effects were seen in cell populations from the humerus. In 6-week-old rats, there was a greater decrease in bone volume, osteoblast number, and osteoblast surface in the proximal tibial metaphysis than that observed in adult rats. Both trabecular thickness and trabecular number were decreased in young rats but remained unaffected in adults. Neither osteoclast number nor surface was affected by unloading. Our results show that the HU-induced decrease in the number of osteoprogenitors observed in vitro parallels the effects of HU on bone volume and osteoblast number in young and old rats in vivo, suggesting that the two may be interdependent. HU also reduced CFU-O colony size in femoral populations indicating a diminished proliferative capacity of osteoblastic colonies.
对在太空飞行的大鼠或后肢卸载（HU）的大鼠进行的实验表明，在这两种情况下，骨质流失都与松质骨和皮质骨的骨体积及成骨细胞表面减少有关。我们推测，成骨细胞骨形成及成骨细胞表面的减少与骨祖细胞数量的减少和/或其后代增殖的降低有关。我们通过评估14天的HU对6周龄和6月龄大鼠股骨近端（卸载）和肱骨近端（正常加载）来源的细胞群体中骨祖细胞（成骨细胞集落形成单位；CFU-O）、成纤维细胞集落形成单位（CFU-F）和碱性磷酸酶阳性CFU（CFU-AP）数量的影响来验证这一假设。为了证实卸载对骨体积和结构的影响，对胫骨近端干骺端进行了静态组织形态计量学参数测量。通过测量CFU-O的大小来评估HU对骨祖细胞增殖的影响。HU对年轻或成年大鼠任何细胞群体中的祖细胞总数（CFU-F）均无影响。在年轻大鼠的股骨细胞群体中，HU使CFU-O减少了71.0%，平均集落大小降低了20%。HU使CFU-AP减少了31.3%。正如预期的那样，肱骨来源的细胞群体中CFU-O或CFU-AP未见变化。在成年大鼠的股骨细胞群体中，HU使CFU-O和CFU-AP分别减少了16.6%和36.6%。同样，肱骨来源的细胞群体未见影响。在6周龄大鼠中，胫骨近端干骺端的骨体积、成骨细胞数量和成骨细胞表面的减少幅度大于成年大鼠。年轻大鼠的小梁厚度和小梁数量均减少，但成年大鼠未受影响。卸载对破骨细胞数量和表面均无影响。我们的结果表明，体外观察到的HU诱导的骨祖细胞数量减少与HU对年轻和老年大鼠体内骨体积和成骨细胞数量的影响相似，提示二者可能相互依赖。HU还降低了股骨细胞群体中CFU-O的集落大小，表明成骨细胞集落的增殖能力减弱。
