Mineralization of the connective tissue: A complex molecular process leading to age-related loss of function

  1. Get@NRC: Mineralization of the connective tissue: A complex molecular process leading to age-related loss of function (Opens in a new window)
DOIResolve DOI: http://doi.org/10.1089/rej.2013.1475
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Journal titleRejuvenation Research
Pages116133; # of pages: 18
Subjectadvanced glycation end product; bone morphogenetic protein; collagen; fibroblast growth factor; fresolimumab; hydroxymethylglutaryl coenzyme A reductase inhibitor; matrix metalloproteinase inhibitor; metelimumab; pioglitazone; procollagen lysine 2 oxoglutarate 5 dioxygenase; protein lysine 6 oxidase; age; aging; article; atherosclerosis; bioinformatics; blood vessel calcification; bone disease; bone mineralization; chronic kidney disease; connective tissue; craniofacial synostosis; cross linking; hormone substitution; human; kidney polycystic disease; nonhuman; nuclear magnetic resonance imaging; optical coherence tomography; ossification; priority journal; protein cross linking; pseudoxanthoma elasticum; rigidity; soft tissue calcification; tissue degeneration; tissue mineralization
AbstractAge-related metastatic mineralization of soft tissues has been considered a passive and spontaneous process. Recent data have demonstrated that calcium salt deposition in soft tissues could be a highly regulated process. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Different mechanisms underlying calcium apatite accumulation are explored with these age-related disorders. In the case of atherosclerotic plaques, oxy-lipids trigger release of the pro-inflammatory cytokines and inflammation that activate calcification processes in aorta intimae. In CKD patients, renal failure alters the balance between calcium and phosphate levels usually regulated by fibroblast growth factor-23 (FGF23), Klotho, and vitamin D, and vascular smooth muscle cells (VSMCs) begin to explore an osteoblastosteoblast-like phenotype. Calcification could affect extracellular matrix along with VSMCs. Collagen is a major component of extracellular matrix and its modifications accumulate with age. The formation of cross-links between collagen fibers is regulated by the action of lysine hydroxylases and lysyl oxidase and could occur spontaneously. Oxidation-induced advanced glycation end products (AGEs) are a major type of spontaneous cross-links that accelerate with age and may result in tissue stiffness, problems with recycling, and potential accumulation of calcium apatite. Applying strategies for clearing the AGEs proposed by de Grey may be more difficult in the highly mineralized extracellular matrix. We performed bioinformatic analysis of the molecular pathways underlying calcification in atherosclerotic and CKD patients, signaling pathways of collagen cross-links formation, and bone mineralization, and we propose new potential targets and review drugs for calcification treatment. © Copyright 2014, Mary Ann Liebert, Inc. 2014.
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AffiliationNational Research Council Canada (NRC-CNRC); National Institute for Nanotechnology (NINT-INNT)
Peer reviewedYes
NPARC number21272148
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Record identifier54d36233-210a-4ac6-898c-301359f9de82
Record created2014-07-23
Record modified2016-05-09
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