Pernow Y, Granberg B, Sääf M, Weidenhielm L
Endocrine and Diabetes Unit, Department of Molecular Medicine, Karolinska Institute and Karolinska University Hospital, Stockholm S-171 76, Sweden.
Calcif Tissue Int. 2006 Feb;78(2):90-7. doi: 10.1007/s00223-005-0158-9. Epub 2006 Feb 6.
The etiology of primary osteoporosis in young and middle-aged men is unknown. We have studied osteoblast function in cells derived from men with idiopathic osteoporosis and in control cells from age-matched men with osteoarthrosis. Osteoblasts were isolated from transiliac bone biopsies. Osteoblast function was measured as vitamin D-stimulated osteocalcin production and production of cytokines and factors involved in osteoclast activation and bone formation. Cell proliferation was measured as (3)H-thymidine incorporation. Parathyroid hormone-related peptide (PTHrP) mRNA was measured using reverse-transcriptase polymerase chain reaction. In osteoporotic men, bone mineral density at the femoral neck was correlated to in vitro production of osteocalcin. Osteoblasts from osteoporotic men produced significantly less osteocalcin after vitamin D stimulation but had increased production of macrophage colony-stimulating factor (M-CSF) compared to controls. The osteocalcin response was negatively correlated to production of M-CSF, interleukin-6, and C-terminal propeptide of type I collagen. Basal (3)H-thymidine incorporation was similar in cells from osteoporotic patients and controls. PTHrP (10(-9 )M) significantly increased cell proliferation in control cells but not in osteoporotic cells. Basal PTHrP mRNA levels were significantly higher in osteoporotic cells than in cells from controls. The results are in agreement with previous histomorphologic studies indicating that men with idiopathic osteoporosis have an osteoblast dysfunction with decreased osteocalcin production and increased production of factors stimulating osteoclast activation. This indicates a catabolic cellular metabolic balance leading to negative bone turnover, resulting in osteoporosis. The cause of such cellular dysfunction needs further evaluation.
中青年男性原发性骨质疏松症的病因尚不清楚。我们研究了来自特发性骨质疏松症男性患者的细胞和成年龄匹配的骨关节炎男性对照细胞中的成骨细胞功能。成骨细胞从髂骨活检组织中分离出来。成骨细胞功能通过维生素D刺激的骨钙素产生以及参与破骨细胞激活和骨形成的细胞因子和因子的产生来衡量。细胞增殖通过³H-胸腺嘧啶核苷掺入来测量。使用逆转录聚合酶链反应测量甲状旁腺激素相关肽（PTHrP）mRNA。在骨质疏松症男性中，股骨颈的骨矿物质密度与体外骨钙素的产生相关。与对照组相比，骨质疏松症男性的成骨细胞在维生素D刺激后产生的骨钙素明显减少，但巨噬细胞集落刺激因子（M-CSF）的产生增加。骨钙素反应与M-CSF、白细胞介素-6和I型胶原C端前肽的产生呈负相关。骨质疏松症患者和对照组细胞的基础³H-胸腺嘧啶核苷掺入相似。PTHrP（10⁻⁹ M）显著增加对照细胞的细胞增殖，但对骨质疏松症细胞无此作用。骨质疏松症细胞中的基础PTHrP mRNA水平显著高于对照组细胞。这些结果与先前的组织形态学研究一致，表明特发性骨质疏松症男性存在成骨细胞功能障碍，骨钙素产生减少，刺激破骨细胞激活的因子产生增加。这表明一种分解代谢的细胞代谢平衡导致负性骨转换，从而导致骨质疏松症。这种细胞功能障碍的原因需要进一步评估。
