Marie P
INSERM_Unité 349, Lariboisière Hospital, Paris, France.
Rev Rhum Engl Ed. 1997 Jan;64(1):44-53.
The cellular mechanisms involved in osteoblast function and bone formation alterations in osteoporosis have been partly elucidated. Recent studies have shown that bone formation abnormalities in various forms of osteopenia result mainly from defective recruitment of osteoblastic cells. These abnormalities in osteoblast function and bone formation are associated with alterations in the expression or production of several growth factors, such as IGFs and TGF-beta, which modulate the proliferation and activity of bone-forming cells. Bone loss related to aging or unloading is characterized by diminished osteoblast proliferation and reduced local concentrations of IGFs and TGF beta. In contrast, estrogen deficiency increases osteoblast proliferation and IGF-I production. These data suggest that alterations in the production of and/or in cell responsiveness to local growth factors may contribute to the bone formation abnormalities seen in these osteopenic disorders. This suggests that preventive or curative treatment with growth factors may be beneficial in osteopenia due predominantly to decreased bone formation. Low doses of IGF-I or TGF-beta have been reported to increase osteoblast recruitment and differentiation, leading to enhanced trabecular bone formation and decreased bone loss in models of osteopenia induced by aging, estrogen deficiency and unloading. A few clinical trials also suggest that low doses of growth factors may stimulate bone formation. Although these findings open up new prospects for the prevention and treatment of osteopenic disorders, progress in this direction awaits the development of factors or analogs that are capable of locally and specifically increasing osteoblast recruitment and differentiation without including side-effects.
骨质疏松症中涉及成骨细胞功能和骨形成改变的细胞机制已部分阐明。最近的研究表明，各种形式的骨质减少中骨形成异常主要源于成骨细胞募集缺陷。成骨细胞功能和骨形成的这些异常与几种生长因子（如胰岛素样生长因子（IGFs）和转化生长因子-β（TGF-β））的表达或产生改变有关，这些生长因子调节骨形成细胞的增殖和活性。与衰老或废用相关的骨质流失的特征是成骨细胞增殖减少以及IGFs和TGF-β局部浓度降低。相反，雌激素缺乏会增加成骨细胞增殖和IGF-I的产生。这些数据表明，局部生长因子的产生和/或细胞对其反应性的改变可能导致这些骨质减少性疾病中出现的骨形成异常。这表明，对于主要由于骨形成减少导致的骨质减少，使用生长因子进行预防性或治疗性治疗可能有益。据报道，低剂量的IGF-I或TGF-β可增加成骨细胞募集和分化，在衰老、雌激素缺乏和废用诱导的骨质减少模型中导致小梁骨形成增强和骨质流失减少。一些临床试验也表明，低剂量的生长因子可能刺激骨形成。尽管这些发现为骨质减少性疾病的预防和治疗开辟了新前景，但朝着这个方向取得进展仍有待开发能够局部和特异性增加成骨细胞募集和分化且无副作用的因子或类似物。
