Bone formation by bone morphogenetic proteins under immune disorders

骨形成除受多种生长因子包括骨形态发生蛋白(BMPs)的控制外，还受多种细胞因子的控制，提示可能受宿主免疫反应的调节。为了测试宿主中的免疫紊乱是否会影响骨形成，我们分析了几个品系的小鼠在BMPs诱导的骨形成中的情况，这些小鼠携带单一突变基因；淋巴增殖基因(LPR)或泛发性淋巴增殖性疾病基因(GLD)，它编码淋巴结病，导致免疫紊乱。将牛骨来源的粗骨形成蛋白注射到小鼠股骨肌肉内，用X射线照相法对异位骨形成进行定量分析。GLD基因的表达和LPR基因的表达具有显著的促进非狼疮易感小鼠品系C3H/HeJ异位成骨的潜力。然而，在易患狼疮的小鼠MRL/MPJ中，LPR基因相当抑制异位骨形成，可能是由于组织学观察到的破骨细胞增加积累所致。这些发现表明，BMPs诱导的骨形成受到与淋巴增殖基因和遗传背景相关的免疫紊乱的影响。

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.