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Investigation of bone disease using isomerized and racemized fragments of type I collagen.

January 1, 2003

Calcif Tissue Int

Abstract In the collagen type I C-telopeptide an aspartyl-glycine site within the sequence AHDGGR is susceptible to molecular rearrangement. In newly synthesized collagen this site is in the native form, denoted alpha L. During aging a spontaneous reaction occurs resulting in three age-modified forms: an isomerized form (beta L) a racemized form (alpha D), and […]

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Breast cancer patients with bone metastases are characterised by increased levels of nonisomerised type I collagen fragments.

January 1, 2003

Breast Cancer Res

Abstract BACKGROUND Fragments of collagen type I containing the epitope AHDGGR (CTX) are generated during bone resorption. The aspartyl-glycine (DG) site within CTX is synthesised in the L-aspartyl peptide (alphaL) form, but converts to the age-modified forms L-isoaspartyl peptide (betaL) and D-aspartyl peptide (alphaD) over time. The purpose of the present study was to test […]

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Matrix metalloproteinase-dependent activation of latent transforming growth factor-beta controls the conversion of osteoblasts into osteocytes by blocking osteoblast apoptosis.

November 15, 2002

J Biol Chem

Abstract Upon termination of bone matrix synthesis, osteoblasts either undergo apoptosis or differentiate into osteocytes or bone lining cells. In this study, we investigated the role of matrix metalloproteinases (MMPs) and growth factors in the differentiation of osteoblasts into osteocytes and in osteoblast apoptosis. The mouse osteoblast cell line MC3T3-E1 and primary mouse calvarial osteoblasts […]

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Synthetic matrix metalloproteinase inhibitors inhibit growth of established breast cancer osteolytic lesions and prolong survival in mice.

June 1, 2002

Clin Cancer Res

Abstract PURPOSE Breast cancer frequently leads to incurable bone metastasis. Essential requirements for the development of bone metastasis are cell-cell and cell-matrix interactions, release of bioactive growth factors and cytokines, and removal of large amounts of bone matrix. Matrix metalloproteinases (MMPs) play an important role in all of these processes, but the possibility of using […]

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Non-enzymatic covalent modifications of proteins: mechanisms, physiological consequences and clinical applications.

January 1, 2002

Matrix Biol

Abstract Given the complexity of the biosynthetic machinery and the delicate chemical composition of proteins, it is remarkable that cells manage to produce and maintain normally functioning proteins under most conditions. However, it is now well known that proteins are susceptible to various non-enzymatic covalent modifications (NECM) under physiological conditions. Such modifications can be of […]

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