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Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance
Journal of bone and mineral research, 2012-09, Vol.27 (9), p.1936-1950
Tang, Simon Y
Herber, Ralf-Peter
Ho, Sunita P
Alliston, Tamara
2012
Details
Autor(en) / Beteiligte
Tang, Simon Y
Herber, Ralf-Peter
Ho, Sunita P
Alliston, Tamara
Titel
Matrix metalloproteinase-13 is required for osteocytic perilacunar remodeling and maintains bone fracture resistance
Ist Teil von
Journal of bone and mineral research, 2012-09, Vol.27 (9), p.1936-1950
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2012
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Like bone mass, bone quality is specified in development, actively maintained postnatally, and disrupted by disease. The roles of osteoblasts, osteoclasts, and osteocytes in the regulation of bone mass are increasingly well defined. However, the cellular and molecular mechanisms by which bone quality is regulated remain unclear. Proteins that remodel bone extracellular matrix, such as the collagen‐degrading matrix metalloproteinase (MMP)‐13, are likely candidates to regulate bone quality. Using MMP‐13–deficient mice, we examined the role of MMP‐13 in the remodeling and maintenance of bone matrix and subsequent fracture resistance. Throughout the diaphysis of MMP‐13–deficient tibiae, we observed elevated nonenzymatic cross‐linking and concentric regions of hypermineralization, collagen disorganization, and canalicular malformation. These defects localize to the same mid‐cortical bone regions where osteocyte lacunae and canaliculi exhibit MMP‐13 and tartrate‐resistant acid phosphatase (TRAP) expression, as well as the osteocyte marker sclerostin. Despite otherwise normal measures of osteoclast and osteoblast function, dynamic histomorphometry revealed that remodeling of osteocyte lacunae is impaired in MMP‐13−/− bone. Analysis of MMP‐13−/− mice and their wild‐type littermates in normal and lactating conditions showed that MMP‐13 is not only required for lactation‐induced osteocyte perilacunar remodeling, but also for the maintenance of bone quality. The loss of MMP‐13, and the resulting defects in perilacunar remodeling and matrix organization, compromise MMP‐13−/− bone fracture toughness and postyield behavior. Taken together, these findings demonstrate that osteocyte perilacunar remodeling of mid‐cortical bone matrix requires MMP‐13 and is essential for the maintenance of bone quality. © 2012 American Society for Bone and Mineral Research.
Sprache
Englisch
Identifikatoren
ISSN: 0884-0431
eISSN: 1523-4681
DOI: 10.1002/jbmr.1646
Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3415585
Format
–
Schlagworte
Acid phosphatase (tartrate-resistant)
,
Animals
,
Biological and medical sciences
,
Biomechanical Phenomena
,
Bone histomorphometry
,
Bone loss
,
Bone mass
,
BONE MATRIX
,
Bone Matrix - diagnostic imaging
,
Bone Matrix - metabolism
,
Bone Matrix - pathology
,
BONE QUALITY
,
Bone Remodeling
,
Bone remodelling
,
Bone Resorption - diagnostic imaging
,
Bone Resorption - pathology
,
Bone Resorption - physiopathology
,
Calcification, Physiologic
,
Collagen
,
Collagen - metabolism
,
Collagenase 3
,
Cross-linking
,
Diaphysis
,
Extracellular matrix
,
Female
,
FRACTURE RESISTANCE
,
Fractures
,
Fractures, Bone - diagnostic imaging
,
Fractures, Bone - enzymology
,
Fractures, Bone - pathology
,
Fractures, Bone - physiopathology
,
Fundamental and applied biological sciences. Psychology
,
Lactation
,
Matrix metalloproteinase
,
Matrix Metalloproteinase 13 - deficiency
,
Matrix Metalloproteinase 13 - metabolism
,
MATRIX METALLOPROTEINASE-13
,
Mechanical properties
,
Mice
,
Molecular modelling
,
Organ Size
,
Osteoblasts
,
Osteoblasts - metabolism
,
Osteoblasts - pathology
,
Osteoclasts
,
Osteoclasts - metabolism
,
Osteoclasts - pathology
,
OSTEOCYTE
,
OSTEOCYTE PERILACUNAR REMODELING
,
Osteocytes
,
Osteocytes - enzymology
,
Osteocytes - pathology
,
Osteogenesis
,
Protein Transport
,
REMODELING
,
Skeleton and joints
,
SOST protein
,
Tibia - diagnostic imaging
,
Tibia - enzymology
,
Tibia - pathology
,
Tibia - physiopathology
,
Vertebrates: osteoarticular system, musculoskeletal system
,
X-Ray Microtomography
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