EFFECTS OF INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA ON OSTEOBLASTIC EXPRESSION OF OSTEOCALCIN AND MINERALIZED EXTRACELLULAR-MATRIX INVITRO
EFFECTS OF INTERLEUKIN-1-BETA AND TUMOR-NECROSIS-FACTOR-ALPHA ON OSTEOBLASTIC EXPRESSION OF OSTEOCALCIN AND MINERALIZED EXTRACELLULAR-MATRIX INVITRO
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DOI：
10.1007/bf00919342
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发表时间：
1992-12-01
期刊：
影响因子：
5.1
通讯作者：
HAUSCHKA, PV
中科院分区：
文献类型：
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作者：
TAICHMAN, RS;HAUSCHKA, PV
成骨细胞在骨对刺激骨吸收和/或抑制骨形成的试剂（包括激素、多肽生长因子和细胞因子）的生物反应期间起关键作用。我们研究了细胞因子白细胞介素-1-β（IL-1 β）和肿瘤坏死因子-α（TNF-α）对成骨细胞增殖和碱性磷酸酶和成骨细胞特异性蛋白骨钙素在矿化环境中的表达的影响。研究了原代大鼠成骨细胞样细胞（ROB）和大鼠（ROS 17/2.8）和人（MG-63）骨肉瘤衍生的成骨细胞系。选择IL-1 β和TNF-α是因为它们在宿主对局部炎症刺激的反应中至关重要。在所有三种融合后骨形成模型系统中观察到IL-1 β和TNF-α对骨钙素合成的定性相似的2 - 3倍抑制。由于在我们的培养方案中产生的骨钙素的浓度容易测量，因此没有必要通过补充1，25（OH）2-维生素D3来增强成骨细胞的骨钙素合成，所述1，25（OH）2-维生素D3是对成骨细胞发挥多效性作用的治疗。在我们的方案的限制下，碱性磷酸酶和矿化在治疗的第14天开始时已经升高，这些表型特性对三天的细胞因子暴露都不敏感。在增殖中注意到差异，其中仅TNF-α刺激ROB细胞中的DNA合成，而两种细胞因子刺激MG-63细胞。IL-1 β和TNF-α未能改变ROS 17/2.8 DNA合成，但在最高剂量（25 pM IL-1 β和1 nM TNF-α）下观察到抑制作用。这些结果进一步支持了这样的观点，即苦参碱介导的成骨细胞调节可以是相对选择性的。
Osteoblasts play a pivotal role during the bioresponse of bone to agents that stimulate bone resorption and/or inhibit bone formation including hormones, polypeptide growth factors, and cytokines. We examined the cytokines interleukin-1-beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) for their effects on osteoblastic proliferation and development and expression of alkaline phosphatase and the osteoblast-specific protein osteocalcin in a mineralizing environment. Primary rat osteoblast-like cells (ROB) and osteoblastic cell lines derived from rat (ROS 17/2.8) and human (MG-63) osteosarcomas were studied. IL-1beta and TNF-alpha were chosen because of their critical importance during the host response to local inflammatory stimuli. Qualitatively similar two- to threefold inhibition of osteocalcin synthesis by IL-1beta and TNF-alpha were observed in all three postconfluent bone-forming model systems. Because of the readily measurable concentrations of osteocalcin produced in our culture protocol, it was not necessary to enhance osteoblastic synthesis of osteocalcin by supplementation with 1,25(OH)2-vitamin D3, a treatment which exerts pleiotropic effects on osteoblasts. Under the constraints of our protocol, where alkaline phosphatase and mineralization were already elevated at the 14-day onset of treatment, neither of these phenotypic properties was sensitive to a three-day cytokine exposure. Differences were noted in proliferation, where only TNF-alpha stimulated DNA synthesis in ROB cells, while both cytokines stimulated MG-63 cells. IL-1beta and TNF-alpha failed to alter ROS 17/2.8 DNA synthesis except at the highest doses (25 pM IL-1beta and 1 nM TNF-alpha) where inhibition was observed. These results further support the view that cytokine-mediated osteoblastic regulation can be relatively selective.