Yamashita Teruhito, Takahashi Naoyuki, Udagawa Nobuyuki
Teruhito Yamashita, Naoyuki Takahashi, Institute for Oral Science, Matsumoto Dental University, 1780 Gobara, Hirooka, Shiojiri, Nagano 399-0781, Japan.
World J Orthop. 2012 Nov 18;3(11):175-81. doi: 10.5312/wjo.v3.i11.175.
Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control of bone-forming osteoblasts. So far, macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent of M-CSF, RANKL, and OPG production. Identification of osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution of osteoclast precursors in bone. Interleukin 34 (IL-34), a novel ligand for c-Fms, plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5a, produced by osteoblasts, enhances osteoclast differentiation by upregulating RANK expression through activation of the non-canonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptor tyrosine-based activation motif signals. Thus, recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.
骨吸收破骨细胞由单核细胞/巨噬细胞谱系在成骨细胞的严格控制下形成。到目前为止，成骨细胞产生的巨噬细胞集落刺激因子（M-CSF）、核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）在破骨细胞分化的调节中起主要作用。最近的研究表明，成骨细胞通过几种独立于M-CSF、RANKL和OPG产生的机制调节破骨细胞生成。体内破骨细胞定向前体的鉴定表明，成骨细胞参与破骨细胞前体在骨中的分布。白细胞介素34（IL-34）是c-Fms的一种新型配体，在维持M-CSF缺陷小鼠破骨细胞定向前体的脾脏储存库中起关键作用。IL-34在破骨细胞生成中也能够替代成骨细胞产生的M-CSF。成骨细胞产生的Wnt5a通过激活非经典Wnt途径上调RANK表达来增强破骨细胞分化。成骨细胞产生的信号素3A通过抑制基于免疫受体酪氨酸的激活基序信号来抑制RANKL诱导的破骨细胞分化。因此，最近的研究结果表明，破骨细胞分化受成骨细胞通过几种不同机制的严格调控。这些新发现的分子有望成为骨相关疾病治疗药物的有前景的靶点。
