Bertolini D R, Strassmann G
Otsuka America Pharmaceutical Co., Ltd., Maryland Research Laboratory, Rockville.
Cytokine. 1991 Sep;3(5):421-7. doi: 10.1016/1043-4666(91)90046-g.
In this study, the ability of recombinant human macrophage (M) and murine granulocyte-macrophage (GM) colony stimulating factor (CSF) to affect both basal and stimulated bone resorption in fetal rat long-bone organ cultures was assessed. It was found that M-CSF does not affect basal bone resorption or bone resorption stimulated by parathyroid hormone, recombinant human interleukin 1 beta, prostaglandin E2 (PGE2), and 1,25 dihydroxy vitamin D3. Specifically, M-CSF at concentrations as high as 30 nM (1 microgram/mL) did not modulate 45Ca release from fetal rat long bones stimulated by these agents. The addition of recombinant murine GM-CSF (at equal molar concentration to M-CSF) also did not affect bone resorption stimulated by parathyroid hormone and interleukin 1 beta. On the other hand, GM-CSF stimulated basal bone resorption over a 120-h period and augmented the resorption mediated by exogenous PGE2 over a 48-h incubation. In addition, GM-CSF was shown to stimulate production of endogenous PGE2 in cultures of bone rudiments. These effects on bone resorption were blocked by the addition of prostaglandin synthesis inhibitors and specific antibodies to murine GM-CSF. These data indicate that M-CSF does not act as a regulator of bone turnover, but GM-CSF may cause bone resorption by stimulating the synthesis of PGE2 in bone.
在本研究中，评估了重组人巨噬细胞（M）集落刺激因子（CSF）和小鼠粒细胞 - 巨噬细胞（GM）集落刺激因子对胎鼠长骨器官培养中基础和刺激后的骨吸收的影响。结果发现，M - CSF不影响基础骨吸收或甲状旁腺激素、重组人白细胞介素1β、前列腺素E2（PGE2）和1,25 - 二羟维生素D3刺激后的骨吸收。具体而言，浓度高达30 nM（1微克/毫升）的M - CSF不会调节这些因子刺激胎鼠长骨释放45Ca。添加重组小鼠GM - CSF（与M - CSF等摩尔浓度）也不影响甲状旁腺激素和白细胞介素1β刺激后的骨吸收。另一方面，GM - CSF在120小时内刺激基础骨吸收，并在48小时孵育期间增强外源性PGE2介导的骨吸收。此外，GM - CSF被证明可刺激骨原基培养物中内源性PGE2的产生。添加前列腺素合成抑制剂和针对小鼠GM - CSF的特异性抗体可阻断这些对骨吸收的作用。这些数据表明，M - CSF不作为骨转换的调节因子，但GM - CSF可能通过刺激骨中PGE2的合成而导致骨吸收。
