Mechanisms Underlying Catabolic and Anabolic Functions of Parathyroid Hormone on Bone by Combination of Culture Systems of Mouse Cells
Mechanisms Underlying Catabolic and Anabolic Functions of Parathyroid Hormone on Bone by Combination of Culture Systems of Mouse Cells
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DOI：
10.1002/jcb.22454
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发表时间：
2010-03-01
影响因子：
4
通讯作者：
Ogata, Naoshi
中科院分区：
文献类型：
--
作者：
Shinoda, Yusuke;Kawaguchi, Hiroshi;Ogata, Naoshi
由于甲状旁腺激素(PTH)连续和间歇性治疗所致的骨吸收和骨形成涉及骨中各种类型的细胞，本研究通过小鼠原代颅骨成骨细胞和骨髓细胞的联合培养系统来研究其潜在的机制。PTH/PTHrP受体(PTH1R)表达和cAMP积聚随着成骨细胞分化程度的增加而增加。在成骨细胞与骨髓细胞的单层共培养中，持续PTH处理可强烈诱导破骨细胞的形成，这与分化的成骨细胞中RANKL的表达有关。在双室培养皿中，间歇性甲状旁腺激素可刺激单层共培养和分离共培养的骨髓细胞层的骨形成，但不能刺激单独培养的骨髓细胞。当骨髓细胞来自胰岛素受体底物-1基因敲除小鼠(IRS-1-/-)或成骨细胞来自PTH1R-/-小鼠时，分离的共培养中伴随着成骨细胞产生IGF-I的刺激被取消。我们认为，分化的成骨细胞很可能是持续性和间歇性甲状旁腺激素的直接靶细胞，而骨髓细胞可能是效应细胞。持续PTH刺激的成骨细胞表达RANKL，RANKL通过细胞间接触促使骨髓前体细胞破骨生成，导致骨吸收；间歇性PTH刺激的成骨细胞分泌IGF-1，通过旁分泌机制激活骨髓成骨前体细胞中的IRS-1，导致骨形成。J.细胞。生物化学。109：755-763,2010。(C)2010年Wiley-Liss公司
Since bone resorption and formation by continuous and intermittent parathyroid hormone (PTH) treatments involve various types of cells in bone, this study examined the underlying mechanism by combining culture systems using mouse primary calvarial osteoblasts and bone marrow cells. The PTH/PTHrP receptor (PTH1R) expression and the cAMP accumulation in response to PTH were increased in accordance with the differentiation of osteoblasts. Osteoclast formation was strongly induced by continuous PTH treatment in the monolayer co-culture of osteoblasts and bone marrow cells, which was associated with RANKL expression in differentiated osteoblasts. Bone formation determined by ALP activity and the type I collagen mRNA expression was stimulated by intermittent PTH treatment in the monolayer co-culture and in the bone marrow cell layer of the separated co-culture in a double chamber dish, but not in the culture of bone marrow cells alone. The stimulation in the separated co-culture, accompanied by IGF-I production by osteoblasts, was abolished when bone marrow cells were derived from knockout mice of insulin-receptor substrate-1 (IRS-1-/-) or when osteoblasts were from PTH1R-/-mice. We conclude that differentiated osteoblasts are most likely the direct target of both continuous and intermittent PTH, while bone marrow cells are likely the effector cells. The osteoblasts stimulated by continuous PTH express RANKL which causes osteoclastogenesis from the precursors in hone marrow via cell-to-cell contact, leading to bone resorption; while the osteoblasts stimulated by intermittent PTH secrete IGF-1 which activates IRS-1 in osteoblast precursors in bone marrow via a paracrine mechanism, leading to bone formation. J. Cell. Biochem. 109: 755-763, 2010. (C) 2010 Wiley-Liss, Inc.