Alsina M, Boyce B F, Mundy G R, Roodman G D
University of Texas Health Science Center at San Antonio, USA.
Stem Cells. 1995 Aug;13 Suppl 2:48-50.
Osteolytic bone destruction and its complications, such as hypercalcemia, pathologic fractures and nerve compression, are the major source of morbidity in patients with multiple myeloma (MM). The bone destruction in MM is due to increased osteoclast activity, but the mechanisms responsible are not entirely clear. We have utilized a human plasma cell leukemia cell line, ARH-77, that has disseminated growth in mice with severe combined immunodeficiency (SCID) and expresses immunoglobulin G kappa (IgG kappa), as a model for human MM. Fifteen SCID mice were irradiated with 400R and 10 of these were injected with 10(6) ARH-77 cells i.v., 24 h after irradiation. Five mice were used as a control group. Development of bone disease was assessed by blood calcium levels, x-rays and histology. Seven out of seven mice that survived irradiation and received ARH-77 cells developed hind limb paralysis 28-35 days after injection. One hundred percent of these mice developed hypercalcemia (1.35-1.46 mmol/l), a mean of five days after becoming paraplegic. Lytic bone lesions were detected by x-ray in all the hypercalcemic mice examined. No lytic lesions or hypercalcemic developed in the controls. Mice were then sacrificed after developing hypercalcemia. Histologic examination of the ARH-77 mice showed infiltration of myeloma cells in the liver and spleen. Marked infiltration by the tumor was found in vertebrae and long bones, with loss of bony trabeculae and increased osteoclast numbers.(ABSTRACT TRUNCATED AT 250 WORDS)
溶骨性骨破坏及其并发症，如高钙血症、病理性骨折和神经受压，是多发性骨髓瘤（MM）患者发病的主要原因。MM中的骨破坏是由于破骨细胞活性增加，但具体机制尚不完全清楚。我们利用一种人类浆细胞白血病细胞系ARH-77，它在严重联合免疫缺陷（SCID）小鼠中呈播散性生长并表达免疫球蛋白G κ（IgG κ），作为人类MM的模型。15只SCID小鼠接受400R照射，其中10只在照射后24小时静脉注射10(6)个ARH-77细胞。5只小鼠作为对照组。通过血钙水平、X射线和组织学评估骨病的发展。7只存活下来并接受ARH-77细胞注射的小鼠中有7只在注射后28 - 35天出现后肢麻痹。这些小鼠中有100%出现高钙血症（1.35 - 1.46 mmol/l），平均在截瘫后5天出现。在所有检测的高钙血症小鼠中通过X射线检测到溶骨性骨病变。对照组未出现溶骨性病变或高钙血症。小鼠出现高钙血症后处死。对ARH-77小鼠的组织学检查显示骨髓瘤细胞浸润肝脏和脾脏。在椎骨和长骨中发现肿瘤明显浸润，骨小梁消失且破骨细胞数量增加。（摘要截断于250字）
