Science Room

Cartilage and Bone Cells

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

Uehara N., Kukita A., Kyumoto-Nakamura Y., Yamaza T., Yasuda H., Kukita T.
Laboratory Investigation, 2017

Here, we the authors show that laminin-332 is expressed in 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 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 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.


Laminins and Nidogens in the Pericellular Matrix of Chondrocytes - Their Role in Osteoarthritis and Chondrogenic Differentiation

Schminke B., Frese J., Bode C., Goldring M.B., Miosge N.
American Society for Investigative Pathology, 2015

This is an investigation of cartilage tissue and isolated chondrocytes in three-dimensional culture obtained from patients with late-stage knee OA and nidogen-2 knockout mice. Chondrogenic progenitor cells (CPCs) produced high levels of laminin-a1, laminin-a5, and nidogen-2 in their pericellular matrix, and laminin-a1 enhanced collagen type II and reduced collagen type I expression by cultured CPCs. Nidogen-2 increased SOX9 gene expression. This study reveals that the influence of the pericellular matrix on CPCs is important for the expression of the major regulator transcription factors, SOX9 and RUNX2. Our novel findings that laminins and nidogen-2 drive CPCs toward chondrogenesis may help in the elucidation of new treatment strategies for cartilage tissue regeneration. In summary, the expression of nidogen-2 and laminin is increased in human OA cartilage, and they act as chondrogenic regulators, especially for CPCs. Laminin also promotes chondrogenesis, enhancing collagen type II, COMP, and aggrecan expression, and down-regulating collagen type I. Therefore, these findings on laminin and nidogen-2 may aid in the elucidation of new treatment options, especially for tissue regeneration.