Maspin Is Involved in Bone Matrix Maturation by Enhancing the Accumulation of Latent TGF-β

Abstract

Maspin, a serine protease inhibitor, is expressed by formative osteoblasts. The repression of maspin expression in osteoblastic cells decreased the level of latent TGF-␤ in the extracellular matrix, whereas the overexpression of maspin increased latent TGF-␤. These findings suggest that maspin plays an important role in bone matrix formation, particularly in the accumulation of latent TGF-␤.Introduction: Maspin is a serine protease inhibitor that exhibits tumor suppressive and anti-angiogenic activities. This study was performed to elucidate a possible role for maspin in bone formation. Materials and Methods:We performed immunohistochemical analysis of the expression of maspin during endochondral ossification. We evaluated the expression of maspin mRNA and protein in ROS 17/2.8 cells and primary rat osteoblastic cells by RT-PCR, immunocytochemistry, and Western blot analysis. We also examined the accumulation of TGF-␤ in the extracellular matrix of cultured ROS 17/2.8 cells after transfection with vectors expressing either maspin or maspin antisense. Results: We observed expression of maspin by active osteoblasts in vivo. Rat osteoblastic cells also expressed maspin mRNA and protein in vitro. Moreover, the accumulation of latent TGF-␤ in the extracellular matrix significantly decreased in cultures exposed to an anti-maspin antibody and when cells were transfected with a maspin antisense-expressing vector. In contrast, accumulation of latent TGF-␤ in the extracellular matrix increased after transfection of cells with a vector expressing maspin. Conclusions: These findings suggest that maspin expressed in active osteoblasts plays an important physiological role during maturation of the bone matrix, and in particular, during the process of accumulation of latent TGF-␤ in the extracellular matrix.

X-ray radiation at low doses stimulates differentiation and mineralization of mouse calvarial osteoblasts

“…OCN is secreted mostly in mature osteoblasts during the stage of matrix calcification (19). Consistent with previous reports (10,20), dynamic and well-regulated mRNA expression patterns of these marker genes were observed depending on the differentiation stage of non-irradiated osteoblasts (data not shown). Our results also strongly support that the mRNA expression patterns of these bone-specific markers were affected differently according to the quantity of irradiation and the testing times examined (5).…”

Differential response to intracellular stress in the skin from osteogenesis imperfecta Brtl mice with lethal and non lethal phenotype: A proteomic approach

“…Since, in bone, maspin was reported to be actively expressed in osteoblasts located in site of active bone formation and remodelling, and to act as a TGFβ modulator [58], its over expression in ML bone cells can cause a disequilibrium between the active and latent form of TGFβ, thus playing a role in bone matrix formation.…”

Possible involvement of maspin in tooth development

“…The cell morphology of ameloblasts and odontoblasts was bizarre, and the alignment of these cells disorganized. It has been recently reported that maspin possesses an activity to enhance the ECM maturation through regulating the accumulation of growth factors (Tokuyama et al 2007). Judging from this report, our phenomena may suggest that the suppression of maspin might result in an inhibition of production and/or maturation of dental matrices.…”

“…It possesses tumor suppressive and anti-angiogenic activities (Shi et al 2001;Zhang et al 2000), which are thought to be mediated by an inhibitory eVect of maspin on two plasminogen activators: uPA and tissue type plasminogen activator (tPA) (Biliran and Sheng 2001;Sheng et al 1998). Meanwhile, we previously reported that maspin expressed by active osteoblasts plays an important role in bone matrix maturation by promoting the accumulation of latent TGF-in ECM (Tokuyama et al 2007). This fact reveals that maspin is one of most important molecules facilitating the eVective accumulation of growth factors and matrix proteins in extracellular matrices in tooth development as well as bone formation.…”