Stromelysin (MMP‐3) Synthesis Is Up‐Regulated in Estrogen‐Deficient Mouse Osteoblasts In Vivo and In Vitro

Sex steroids are important regulators of bone cell function and osteoblast‐derived matrix metalloproteinases (MMPs) are key mediators of bone resorption during the initial stage of osteoid removal prior to osteoclast attachment. To investigate the mechanism of bone loss following estrogen deficiency...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of bone and mineral research Vol. 14; no. 11; pp. 1880 - 1890
Main Authors:	Breckon, Jeremy J. W., Papaioannou, Stelios, Kon, Luke W. M., Tumber, Anthony, Hembry, Rosalind M., Murphy, Gillian, Reynolds, John J., Meikle, Murray C.
Format:	Journal Article
Language:	English
Published:	Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01-11-1999 American Society for Bone and Mineral Research
Subjects:	Animals Biological and medical sciences Blotting, Northern - methods Cells, Cultured Collagenases - analysis Collagenases - genetics Diseases of the osteoarticular system Estrogens - metabolism Femur Head - cytology Femur Head - pathology Lumbar Vertebrae - cytology Lumbar Vertebrae - pathology Matrix Metalloproteinase 2 - analysis Matrix Metalloproteinase 2 - genetics Matrix Metalloproteinase 3 - analysis Matrix Metalloproteinase 3 - biosynthesis Matrix Metalloproteinase 3 - genetics Matrix Metalloproteinase 9 - analysis Matrix Metalloproteinase 9 - genetics matrix metalloproteinases Medical sciences Mice Osteoblasts - cytology Osteoblasts - metabolism Osteoporosis. Osteomalacia. Paget disease Ovariectomy Reverse Transcriptase Polymerase Chain Reaction - methods Space life sciences Tissue Inhibitor of Metalloproteinase-1 - genetics Tissue Inhibitor of Metalloproteinase-2 - genetics tissue inhibitors of matrix metalloproteinases Up-Regulation Enzyme Pathogenesis Deficiency Estrogen Rodentia Diseases of the osteoarticular system 17β-Estradiol Enzyme inhibitor Metalloendopeptidases Bone disease Biosynthesis Gene expression Ovarian hormone Osteoarticular system Peptidases Osteoporosis Vertebrata Mammalia Mouse Animal Osteoblast Hydrolases Bone Sex steroid hormone
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Sex steroids are important regulators of bone cell function and osteoblast‐derived matrix metalloproteinases (MMPs) are key mediators of bone resorption during the initial stage of osteoid removal prior to osteoclast attachment. To investigate the mechanism of bone loss following estrogen deficiency, we examined the effects of estrogen on osteoblast synthesis of MMPs and tissue inhibitor of metalloproteinases (TIMPs). Immunolocalization in mouse bone samples ex vivo and primary mouse osteoblast (MOB) cultures was used to document the synthesis of mouse interstitial collagenase (MMP‐13), stromelysin‐1 (MMP‐3), gelatinase‐A (MMP‐2), and gelatinase‐B (MMP‐9). Endosteal bone lining cells from distal femoral head and lumbar vertebral body showed an increase in the pattern of synthesis of stromelysin‐1 following ovariectomy, compared with sham‐operated controls; the synthesis of other MMPs was unaffected. The expression of all classes of MMPs and TIMP‐1 and TIMP‐2 by MOB in culture was demonstrated by reverse transcriptase‐polymerase chain reaction. Following the withdrawal of 17β‐estradiol, MOB cultures showed a significant increase in the number of cells synthesizing stromelysin‐1; this effect was enhanced by stimulation with either interleukin‐1 or interleukin‐6. Northern blot analysis showed only a slight increase in stromelysin‐1 mRNA message following the withdrawal of 17β‐estradiol. Our data show an unexpected up‐regulation of stromelysin‐1 synthesis by osteoblasts both in vivo and in vitro following estrogen withdrawal. Although this effect was not reflected in a significant change in stromelysin‐1 mRNA expression in vitro, there is evidence to suggest a role for this enzyme in the early stages of bone loss during the pathogenesis of osteoporosis.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0884-0431 1523-4681
DOI:	10.1359/jbmr.1999.14.11.1880