Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments

In this article, the authors show that laminin 332 is expressed in primary osteoblasts, and is implicated in the regulation of osteoclast differentiation. Immunofluorescence analysis and RT-PCR analysis indicated specific expression of laminin 332 in osteoblast-like cells localized on the bone surface. Laminin 332 markedly inhibited osteoclastogenesis induced by receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) when bone marrow-derived macrophages (BMMs) were cultured on laminin 332-coated plates. Laminin 332 also blocked RANKL-induced activation of mitogen-activated protein kinases (MAPKs) (ERK, JNK, and p38) and expression of NFATc1, c-Fos, and c-Jun. Laminin 332 suppressed osteoclast differentiation while retaining macrophage phenotypes, including nonspecific esterase activity and gene expression of lysozyme and EGF-like module-containing mucin-like hormone receptor-like 1 (Emr1). Furthermore, the treatment of primary osteoblasts with osteoclastogenic factors dramatically suppressed the expression of laminin 332. These findings suggest that laminin 332 produced by osteoblasts in bone tissues has a pivotal role in controlling normal bone remodeling through suppressing osteoclastogenesis.