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Matrix metalloproteinase-12 (MMP-12) in osteoclasts: new lesson on the involvement of MMPs in bone resorption.

January 1, 2004

Bone

Abstract Osteoclasts require matrix metalloproteinase (MMP) activity and cathepsin K to resorb bone, but the critical MMP has not been identified. Osteoclasts express MMP-9 and MMP-14, which do not appear limiting for resorption, and the expression of additional MMPs is not clear. MMP-12, also called metalloelastase, is reported only in a few cells, including tissue […]

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Role of gastrointestinal hormones in postprandial reduction of bone resorption.

December 1, 2003

J Bone Miner Res

Abstract UNLABELLED Collagen type I fragments, reflecting bone resorption, and release of gut hormones were investigated after a meal. Investigations led to a dose escalation study with glucagon like peptide-2 (GLP-2) in postmenopausal women. We found a dose-dependent effect of GLP-2 on the reduction of bone resorption. INTRODUCTION The C-terminal telopeptide region of type I […]

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Biglycan deficiency interferes with ovariectomy-induced bone loss.

December 1, 2003

J Bone Miner Res

Abstract UNLABELLED Biglycan is a matrix proteoglycan with a possible role in bone turnover. In a 4-week study with sham-operated or OVX biglycan-deficient or wildtype mice, we show that biglycan-deficient mice are resistant to OVX-induced trabecular bone loss and that there is a gender difference in the response to biglycan deficiency. INTRODUCTION Biglycan (bgn) is […]

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Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expression.

November 7, 2003

J Biol Chem

Abstract Although RANK-L is essential for osteoclast formation, factors such as transforming growth factor-beta (TGF-beta) are potent modulators of osteoclastogenic stimuli. To systematically investigate the role of TGF-beta in human osteoclastogenesis, monocytes were isolated from peripheral blood by three distinct approaches, resulting in either a lymphocyte-rich, a lymphocyte-poor, or a pure osteoclast precursor (CD14-positive) cell […]

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Estradiol enhances osteolytic lesions in mice inoculated with human estrogen receptor-negative MDA-231 breast cancer cells in vivo.

March 1, 2003

Breast Cancer Res Treat

Abstract The effect of 17-beta-estradiol (E2) on the induction of osteolytic lesions by estrogen receptor (ER)-negative breast cancer cells was investigated in 4-week-old female nude mice. Exposure to exogenous E2 was found to increase osteolytic areas on radiographs up to 5.3 times in mice inoculated intracardially with MDA-231 human breast cancer cells. The MDA-231 cells […]

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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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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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