Bone formation by bone morphogenetic proteins under immune disorders

除了骨形态发生蛋白（BMPs）等几种生长因子外，骨形成还受到细胞因子的控制，这表明骨形成受到宿主免疫反应的调节。为了测试宿主的免疫紊乱是否影响骨形成，我们分析了几种携带单一突变基因的小鼠中BMP诱导的骨形成;淋巴增殖基因（lpr）或全身性淋巴增殖性疾病基因（gld），其编码淋巴结病，导致免疫紊乱。将牛骨来源的BMP粗品注射到这些小鼠的股骨肌肉中，然后通过使用X射线摄影进行异位骨形成的定量分析。gld基因的表达和lpr基因在较小程度上的表达具有显著的增强非狼疮易感小鼠品系C3 H/HeJ中异位骨形成的潜力。然而，在狼疮倾向的小鼠品系MRL/MpJ中，lpr基因相当抑制异位骨形成，这可能是由于组织学观察到的破骨细胞的积累增强。这些发现表明BMP诱导的骨形成受到与淋巴细胞增殖基因和遗传背景相关的免疫疾病的影响。

Bone formation is under the controls of cytokines in addition to several growth factors including bone morphogenetic proteins (BMPs), suggesting to be regulated by host immune response. To test whether immune disorders in the host influence the bone formation, we analyzed the BMPs-induced bone formation in several strains of mice bearing a single mutation gene; lymphoproliferation gene (lpr) or generalized lymphoproliferative disease gene (gld), which encodes lymphadenopathy, resulting in immune disorders. Crude BMPs derived from bovine bone were injected into femur muscle of these mice, and then quantitative analysis of the ectopic bone formation by using X-ray photography was performed. The expression of the gld gene and to lesser extent the lpr gene had striking potential to enhance the ectopic bone formation in a non-lupus-prone strain of mice, C3H/HeJ. However, in a lupus-prone strain of mice, MRL/MpJ, the lpr gene rather inhibited the ectopic bone formation, possibly due to the enhanced accumulation of osteoclasts histologically observed. These findings indicate that the BMPs-induced bone formation is influenced by immune disorders relevant to lymphoproliferation genes and genetic backgrounds.