OPERATION OF AN INFRARED BEAMLINE DEDICATED TO STUDY OF BIO MEDICAL PROBLEMS

作为检查软骨下骨发育的模型，我们 正在检查患骨硬化症的小鼠（OP/OP小鼠）的关节。 在骨质疏松症中，破骨细胞形成减少， 吸收，导致骨的净过度生长。 OP/OP鼠标 由于CSF-1（集落刺激因子）的改变， 因子-1）基因。 这种突变，插入一个胸苷262碱基 在CSF-1基因中的ATG起始密码子下游对，导致 移码和提前终止密码子的引入。 作为 结果，突变的基因编码截短的蛋白质产物，约 60个氨基酸，缺乏生物活性。 CSF-1正常 刺激破骨细胞祖细胞分化为 破骨细胞，也可以调节成熟的破骨细胞。 在OP/OP 在小鼠中，CSF-1的缺乏导致骨硬化症，这是由于 破骨细胞数量减少;产生的骨不能被吸收。 斯坦利博士实验室和其他地方的研究表明， 自发老化或将人重组CSF-1注射入OP 小鼠从出生3天起，能够恢复骨干骨 (i.e.股骨干中的骨）到更正常的组织学，但是 软骨下骨仍为岩质。 哈尔曼医生和斯坦利医生 检查巨噬细胞和破骨细胞群体随着时间的推移， 老化和CSF-1处理的小鼠中的软骨下骨和骨干骨。 在 此外，上覆关节软骨的组织学状态 将进行检查，以确定岩质软骨下骨是否 与上覆关节软骨的退化有关。

As a model for examining the development of subchondral bone, we are examining the joints of mice who are osteopetrotic (op/op mice). In osteoporosis, reduced osteoclast formation prevents bone resorption, leading to a net overgrowth of bone. The op/op mouse is osteopetrotic due to an alteration in the CSF-1 (Colony Stimulating Factor-1) gene. This mutation, the insertion of a thymidine 262 base pairs downstream of the ATG start codon in the CSF-1 gene, leads to a frame shift and the introduction of a premature stop codon. As a result, the mutated gene encodes a truncated protein product of about 60 amino acids, which lacks biological activity. CSF-1 normally stimulates the differentiation of osteoclast progenitors into osteoclasts and may also regulate mature osteoclasts. In the op/op mouse, the lack of CSF-1 leads to osteopetrosis due to a marked reduction in osteoclast numbers; the bone produced cannot be resorbed. Studies in Dr. Stanley's lab and elsewhere have shown that either spontaneous aging or injections of human recombinant CSF-1 into op mice from 3 days of life, is capable of reverting diaphyseal bone (i.e. bone in the shaft of the femur) to more normal histology, but subchondral bone remains petrotic. Drs. Hamerman and Stanley will examine the macrophage and osteoclast populations over time in the subchondral and diaphyseal bone in aging and CSF-1 treated mice. In addition, the histologic state of the overlying articular cartilage will be examined to determine if petrotic subchondral bone is associated with degeneration of the overlying articular cartilage.