Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-Like receptor ligands and TNF-α
Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to Toll-Like receptor ligands and TNF-α
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DOI：
10.4049/jimmunol.171.10.5130
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发表时间：
2003-11-15
影响因子：
4.4
通讯作者：
Yamazaki, H
中科院分区：
文献类型：
--
作者：
Hayashi, SI;Yamada, T;Yamazaki, H
破骨细胞来源于造血干细胞，在骨吸收和骨重建中起重要作用。多核破骨细胞与骨基质紧密结合，而在培养中具有分化成破骨细胞潜能的前体细胞分布广泛。在这项研究中，我们评估了骨髓（BM）和髓外器官中破骨细胞前体的特征，如它们对Toll样受体（TLR）配体和TNF-α的反应性所示。骨髓中前体细胞破骨细胞的发育被CpG寡核苷酸（TLR 9的配体）抑制，但不被LPS（TLR 4的配体）抑制。在M-CSF存在下，由TNF-α以及NF-κ B配体的受体激活剂诱导BM破骨细胞。脾破骨细胞前体，即使在破骨细胞缺陷型骨硬化小鼠中，在暴露于TNF-α或NF-κ B配体的受体激活剂后分化为成熟的破骨细胞。然而，脾破骨细胞生成被LPS和CpG抑制。腹膜前体的破骨细胞生成不仅受到这些TLR配体的抑制，还受到TNF-α的抑制。TLR 2的配体肽聚糖的作用与LPS的作用相似。用M-CSF预培养的BM细胞的特征在于具有介于脾和腹腔前体细胞之间的中间特征。总之，这些发现表明，破骨细胞前体是不相同的组织检查。要解决的问题，为什么成熟的破骨细胞只发生在与骨，我们可以表征不仅破骨细胞发生的微环境，但也破骨细胞前体本身在髓内和髓外组织。
Osteoclasts are derived from hemopoietic stem cells and play critical roles in bone resorption and remodeling. Multinucleated osteoclasts are attached tightly to bone matrix, whereas precursor cells with the potential to differentiate into osteoclasts in culture are widely distributed. In this study, we assessed the characteristics of osteoclast precursors in bone marrow (BM) and in extramedullary organs as indicated by their responsiveness to ligands for Toll-like receptors (TLRs) and to TNF-alpha. Development of osteoclasts from precursor cells in the BM was inhibited by CpG oligonucleotides, a ligand for TLR9, but not by LPS, a ligand for TLR4. BM osteoclasts were induced by TNF-alpha as well as receptor activator of NF-kappaB ligand in the presence of M-CSF. Splenic osteoclast precursors, even in osteoclast-deficient osteopetrotic mice, differentiated into mature osteoclasts following exposure to TNF-alpha or receptor activator of NF-kappaB ligand. However, splenic osteoclastogenesis was inhibited by both LPS and CpG. Osteoclastogenesis from peritoneal precursors was inhibited by not only these TLR ligands but also TNF-alpha. The effects of peptidoglycan, a ligand for TLR2, were similar to those of LPS. BM cells precultured with M-CSF were characterized with intermediate characteristics between those of splenic and peritoneal cavity precursors. Taken together, these findings demonstrate that osteoclast precursors are not identical in the tissues examined. To address the question of why mature osteoclasts occur only in association with bone, we may characterize not only the microenvironment for osteoclastogenesis, but also the osteoclast precursor itself in intramedullary and extramedullary tissues.