ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing

Rehn, Anders; Birch, Mark; Karlström, Erik; Wendel, Mikael; Lind, Thomas

doi:10.1016/j.bone.2007.04.187

Cited by 34 publications

(28 citation statements)

References 37 publications

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“…In line with this, we and others have also shown that Adamts1 is found in osteogenic cells both in vitro and in vivo [8,9]. In efforts to begin to unravel the mechanism behind how increased ADAMTS1 expression affects osteoblast performance, we found that ADAMTS1 increases osteoblast 3D growth in fibrillar collagen type I gels and that this effect is dependent on its metalloproteinase activity [10]. Mice lacking Adamts1 are smaller, suggesting a possible involvement in bone growth [11], but mice lacking either Adamts2, 4, 5, 9 or 20 show no apparent skeletal phenotype.…”

Section: Introductionsupporting

confidence: 77%

“…Notably, the full-length and mature secreted forms of Adamts1 protein are 115 and 90 kDa, respectively, but it is known to appear in a range of smaller degradation products in vitro [10,18]. We previously showed that osteoblastic ADAMTS1 participated in processing of collagen type I in vitro by producing fragments of around 50 kDa [10]. Here, a Western blot analysis of the collagen type I presented a normal pattern indicating that no unusual protein degradation had occurred during bone protein preparation.…”

Section: Tg Mice Have Increased Adamts1 Protein In Bone Tissuementioning

confidence: 99%

“…The bones from all animals were sectioned in the same orientation in order to make comparable sections. For protein localization, sections were incubated with rabbit anti-Adamts1 (1:200, polyclonal peptide-generated) recognizing the metalloproteinase domain of human ADAMTS1, ATScat (gb: AAF15317) [10] or a rabbit anti-mouse Adamts1 (1:400, Santa Cruz 5468, Santa Cruz, CA, USA). Visualization of the antibodies was achieved by incubation with secondary biotinylated antibody at a dilution of 1:200 in 10% serum and phosphate-buffered saline followed by an avidin-biotin-peroxidase complex incubation using the VECTASTAIN Ò ABC kit (Vector Laboratories, Burlingame, CA, USA) and the substrate diaminobenzidine tetrahydrochloride (DAB) (Dako, Glostrup, Denmark).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Over-expression of Adamts1 in mice alters bone mineral density

Jonsson

Andersén

et al. 2011

J Bone Miner Metab

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ADAMTS1, a secreted multifunctional metalloproteinase with disintegrin and thrombospondin motifs, is an early response gene of parathyroid hormone (PTH) in osteoblasts. Mice engineered to lack Adamts1 are smaller compared to wild-type (WT) mice and ADAMTS1 metalloproteinase activity has been shown to increase osteoblastic growth in collagen gels. However, there are no reports investigating the consequence of Adamts1 over-expression on bone tissue in vivo. Here, we analyze bones of female and male transgenic (TG) mice over-expressing mouse Adamts1 using peripheral quantitative computed tomography to evaluate its effect on bone shape and mineral density. Western blotting of protein extracts and immunohistochemistry of bone sections reveal increased presence of Adamts1 protein in TG bones compared to WT bones. Phenotypic analyses of femur show that female TG mice have reduced metaphyseal total density, trabecular bone mineral density and trabecular mineral content. In contrast, male TG mice which were without changes in the metaphysis showed increased total density and cortical density at the mid-diaphysis cortical site. Female TG mice showed no significant changes at the cortical site compared to WT mice. Furthermore, diaphyseal endosteal compartment was only affected in male TG mice. Along these lines, Adamts1 increased blood levels of PTH only in females whereas it reduced osteocalcin levels only in males. These results reveal that Adamts1 has an impact on bone mineral density and thus further confirm Adamts1 as a potent regulator of bone remodeling.

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Section: Introductionsupporting

confidence: 77%

Section: Tg Mice Have Increased Adamts1 Protein In Bone Tissuementioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

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Over-expression of Adamts1 in mice alters bone mineral density

Jonsson

Andersén

et al. 2011

J Bone Miner Metab

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“…1,2 Mice with Adamts1-null mutation exhibit urogenital defects and female infertility because of impaired remodeling of ovarian extracellular matrix (ECM), but ovarian steroid production and lactation are normal. [3][4][5] A range of ECM proteins have been identified as potential ADAMTS1 substrates, including collagens, 6 nidogen, 7 and syndecan-4 8 ; however, the proteoglycans versican and aggrecan have been consistently shown to be key ADAMTS1 targets. 4,9,10 ADAMTS1 processing of versican is important in cell migration during wound healing, 11 endothelial cell invasion, 12 and remodeling of cardiac jelly ECM during heart morphogenesis.…”

mentioning

confidence: 99%

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Ricciardelli

Frewin

Tan

et al. 2011

The American Journal of Pathology

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The A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of proteins is composed of extracellular metalloproteases, including ADAMTS1, originally identified in cachexigenic colon cancer cells. 1,2 Mice with Adamts1-null mutation exhibit urogenital defects and female infertility because of impaired remodeling of ovarian extracellular matrix (ECM), but ovarian steroid production and lactation are normal. 3-5 A range of ECM proteins have been identified as potential ADAMTS1 substrates, including collagens, 6 nidogen, 7 and syndecan-4 8 ; however, the proteoglycans versican and aggrecan have been consistently shown to be key ADAMTS1 targets. 4,9,10 ADAMTS1 processing of versican is important in cell migration during wound healing, 11 endothelial cell invasion, 12 and remodeling of cardiac jelly ECM during heart morphogenesis. 13 These observations indicate that ADAMTS1 mediates acute regulated tissue remodeling processes that occur in development and in adult reproductive tissues, but also in cancer growth and metastasis.Emerging evidence associates ADAMTS1 expression with metastatic potential. Elevated expression of ADAMTS1 is characteristic of breast cancer cell lines 14,15 and human breast cancers with high bone metastatic potential. 16 Likewise, local invasion and lymph node metastasis of pancreatic cancer is associated with elevated Adamts1. 17 Overexpression of full-length ADAMTS1 in

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“…Rock et al compared the ADAMTS-1 expression of lung cancer with surrounding normal tissue and found higher expression in tumor cells (32). Parathyroid hormone (PTH) was able to up-regulate ADAMTS-1 expression and increase osteoblastic activities via the type I collagen processing (33), indicating the active role of ADAMTS-1 in bone microenviroment. We are presently verifying if ADAMTS-1 could be associated with bone metastasis.…”

Section: Discussionmentioning

confidence: 99%

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

et al. 2010

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Abstract. Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin ß 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

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ADAMTS-1 increases the three-dimensional growth of osteoblasts through type I collagen processing

Cited by 34 publications

References 37 publications

Over-expression of Adamts1 in mice alters bone mineral density

Over-expression of Adamts1 in mice alters bone mineral density

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer

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