Suda T, Kobayashi K, Jimi E, Udagawa N, Takahashi N
Department of Biochemistry, School of Dentistry, Showa University, Tokyo 142-8555, Japan.
Novartis Found Symp. 2001;232:235-47; discussion 247-50. doi: 10.1002/0470846658.ch16.
Osteoclasts develop from haemopoietic cells of the monocyte-macrophage lineage. Osteoblasts or stromal cells are essentially involved in osteoclastogenesis through cell-cell interaction with osteoclast progenitor cells. Recent findings indicate that osteoblasts/stromal cells express osteoclast differentiation factor (ODF, also called RANKL, TRANCE and OPGL) as a membrane-associated factor in response to several osteotropic factors to support osteoclast differentiation. ODF is a new member of the tumour necrosis factor (TNF) ligand family. Osteoclast precursors, which express RANK, a TNF receptor family member, recognize ODF through cell-cell interactions with osteoblasts/stromal cells, and differentiate into osteoclasts in the presence of macrophage colony-stimulating factor (M-CSF). Osteoclastogenesis inhibitory factor (OCIF, also called OPG), is a secreted TNF receptor, which acts as a decoy receptor for ODF. ODF is responsible for inducing not only differentiation, but also activation of osteoclasts. Interleukin 1 alpha (IL-1 alpha) can be substituted for ODF in inducing the activation of osteoclasts. Recently, it was shown that mouse TNF alpha stimulated the differentiation of M-CSF-dependent mouse bone marrow macrophages into osteoclasts in the presence of M-CSF without any help of osteoblasts/stromal cells. Osteoclast formation induced by TNF alpha was inhibited by antibodies against TNF type 1 receptor (TNFR1) or TNFR2, but not by OCIF. Osteoclasts induced by TNF alpha formed resorption pits on dentine slices only in the presence of IL-1 alpha. These results demonstrate that TNF alpha stimulates osteoclast differentiation through a mechanism independent of the ODF-RANK interaction. TNF alpha and IL-1 alpha may play an important role in pathological bone resorption due to inflammation.
破骨细胞由单核细胞 - 巨噬细胞系的造血细胞发育而来。成骨细胞或基质细胞通过与破骨细胞祖细胞的细胞间相互作用，在破骨细胞生成过程中发挥重要作用。最近的研究发现，成骨细胞/基质细胞在多种促骨因子的作用下，会表达一种膜相关因子——破骨细胞分化因子（ODF，也称为RANKL、TRANCE和OPGL），以支持破骨细胞的分化。ODF是肿瘤坏死因子（TNF）配体家族的新成员。表达TNF受体家族成员RANK的破骨细胞前体，通过与成骨细胞/基质细胞的细胞间相互作用识别ODF，并在巨噬细胞集落刺激因子（M-CSF）存在的情况下分化为破骨细胞。破骨细胞生成抑制因子（OCIF，也称为OPG）是一种分泌型TNF受体，它作为ODF的诱饵受体发挥作用。ODF不仅负责诱导破骨细胞的分化，还能促使其激活。白细胞介素1α（IL-1α）在诱导破骨细胞激活方面可以替代ODF。最近的研究表明，在M-CSF存在的情况下，小鼠TNFα能在没有成骨细胞/基质细胞帮助的情况下，刺激依赖M-CSF的小鼠骨髓巨噬细胞分化为破骨细胞。TNFα诱导的破骨细胞形成受到抗1型TNF受体（TNFR1）或TNFR2抗体的抑制，但不受OCIF的抑制。TNFα诱导形成的破骨细胞仅在IL-1α存在的情况下，才能在牙本质切片上形成吸收陷窝。这些结果表明，TNFα通过一种独立于ODF-RANK相互作用的机制刺激破骨细胞分化。TNFα和IL-1α可能在炎症导致的病理性骨吸收中发挥重要作用。
