Department of Hematology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, China; Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Biochem Biophys Res Commun. 2013 Nov 1;440(4):545-50. doi: 10.1016/j.bbrc.2013.09.098. Epub 2013 Oct 5.
Interleukin (IL)-3, a multilineage hematopoietic growth factor, is implicated in the regulation of osteoclastogenesis. However, the role of IL-3 in osteoclastogenesis remains controversial; whereas early studies showed that IL-3 stimulates osteoclastogenesis, recent investigations demonstrated that IL-3 inhibits osteoclast formation. The objective of this work is to further address the role of IL-3 in osteoclastogenesis. We found that IL-3 treatment of bone marrow cells generated a population of cells capable of differentiating into osteoclasts in tissue culture dishes in response to the stimulation of the monocyte/macrophage-colony stimulating factor (M-CSF) and the receptor activator of nuclear factor kappa B ligand (RANKL). The IL-3-dependent hematopoietic cells were able to further proliferate and differentiate in response to M-CSF stimulation and the resulting cells were also capable of forming osteoclasts with M-CSF and RANKL treatment. Interestingly, IL-3 inhibits M-CSF-/RANKL-induced differentiation of the IL-3-dependent hematopoietic cells into osteoclasts. The flow cytometry analysis indicates that while IL-3 treatment of bone marrow cells slightly affected the percentage of osteoclast precursors in the surviving populations, it considerably increased the percentage of osteoclast precursors in the populations after subsequent M-CSF treatment. Moreover, osteoclasts derived from IL-3-dependent hematopoietic cells were fully functional. Thus, we conclude that IL-3 plays dual roles in osteoclastogenesis by promoting the development of osteoclast progenitors but inhibiting the osteoclastogenic process. These findings provide a better understanding of the role of IL-3 in osteoclastogenesis.
白细胞介素 (IL)-3 是一种多谱系造血生长因子，参与调节破骨细胞生成。然而，IL-3 在破骨细胞生成中的作用仍存在争议；尽管早期研究表明 IL-3 刺激破骨细胞生成，但最近的研究表明 IL-3 抑制破骨细胞形成。本工作的目的是进一步探讨 IL-3 在破骨细胞生成中的作用。我们发现，IL-3 处理骨髓细胞可在组织培养皿中产生一群细胞，这些细胞能够在单核细胞/巨噬细胞集落刺激因子 (M-CSF) 和核因子 kappa B 配体受体激活剂 (RANKL) 的刺激下分化为破骨细胞。IL-3 依赖性造血细胞能够进一步增殖和分化，对 M-CSF 刺激作出反应，并且所得细胞在 M-CSF 和 RANKL 处理下也能够形成破骨细胞。有趣的是，IL-3 抑制 M-CSF/RANKL 诱导的 IL-3 依赖性造血细胞向破骨细胞的分化。流式细胞术分析表明，虽然 IL-3 处理骨髓细胞对存活群体中的破骨细胞前体百分比略有影响，但在随后的 M-CSF 处理后，破骨细胞前体百分比明显增加。此外，源自 IL-3 依赖性造血细胞的破骨细胞具有完全的功能。因此，我们得出结论，IL-3 在破骨细胞生成中发挥双重作用，一方面促进破骨细胞前体的发育，另一方面抑制破骨细胞生成过程。这些发现为理解 IL-3 在破骨细胞生成中的作用提供了更好的认识。
