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

Research output: Contribution to journalArticle

Abstract

Laminin-332 (Lm-332), a major basement membrane protein, has been shown to provide a niche for some stem cells. Here, we found that Lm-332 was expressed in osteoblasts, and is implicated in the regulation of osteoclast differentiation. Immunofluorescence analysis of laminin-β3, a unique component of Lm-332, indicated specific expression of laminin-β3 in osteoblast-like cells localized on bone surface. RT-PCR analysis confirmed that α3, β3, and 2 chains of Lm-332 were all expressed in primary osteoblasts prepared from mouse calvaria. Lm-332 markedly inhibited osteoclastogenesis induced by receptor activator of nuclear factor kappa B (NF-B) ligand (RANKL) when bone marrow-derived macrophages (BMMs) were cultured on Lm-332-coated plates. Lm-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. Lm-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 expression of Lm-332. These findings suggest that Lm-332 produced by osteoblasts in bone tissues has a pivotal role in controlling normal bone remodeling through suppressing osteoclastogenesis.

Original languageEnglish
Pages (from-to)1235-1244
Number of pages10
JournalLaboratory Investigation
Volume97
Issue number10
DOIs
Publication statusPublished - Oct 1 2017

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Osteoblasts
Osteogenesis
Bone and Bones
Laminin
Osteoclasts
Macrophages
kalinin
RANK Ligand
Stem Cell Niche
Carboxylesterase
Bone Remodeling
p38 Mitogen-Activated Protein Kinases
Mucins
Muramidase
Epidermal Growth Factor
Basement Membrane
Skull
Fluorescent Antibody Technique
Membrane Proteins
Hormones

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

Cite this

Osteoblast-derived Laminin-332 is a novel negative regulator of osteoclastogenesis in bone microenvironments. / Uehara, Norihisa; Kukita, Akiko; Kyumoto, Yukari; Yamaza, Takayoshi; Yasuda, Hisataka; Kukita, Toshio.

In: Laboratory Investigation, Vol. 97, No. 10, 01.10.2017, p. 1235-1244.

Research output: Contribution to journalArticle

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