- Authors:
-
- Szabova, L. ;
- Yamada, S.S. ;
- Wimer, H. ;
- Chrysovergis, K. ;
-
Ingvarsen, S.
;
Close
0000-0001-7800-6443
Behrendt Group, BRIC, Faculty of Health and Medical Sciences, Københavns Universitet - Behrendt, N. ;
- Engelholm, L.H. ;
- Holmbeck, K.
- DOI:
- 10.1359/jbmr.090510
- Abstract:
- Skeletal formation is dependent on timely recruitment of skeletal stem cells and their ensuing synthesis and remodeling of the major fibrillar collagens, type I collagen and type II collagen, in bone and cartilage tissues during development and postnatal growth. Loss of the major collagenolytic activity associated with the membrane-type 1 matrix metalloproteinase (MT1-MMP) results in disrupted skeletal development and growth in both cartilage and bone, where MT1-MMP is required for pericellular collagen dissolution. We show here that reconstitution of MT1-MMP activity in the type II collagen-expressing cells of the skeleton rescues not only diminished chondrocyte proliferation, but surprisingly, also results in amelioration of the severe skeletal dysplasia associated with MT1-MMP deficiency through enhanced bone formation. Consistent with this increased bone formation, type II collagen was identified in bone cells and skeletal stem/progenitor cells of wildtype mice. Moreover, bone marrow stromal cells isolated from mice expressing MT1-MMP under the control of the type II collagen promoter in an MT1-MMP-deficient background showed enhanced bone formation in vitro and in vivo compared with cells derived from nontransgenic MT1-MMP-deficient littermates. These observations show that type II collagen is not stringently confined to the chondrocyte but is expressed in skeletal stem/progenitor cells (able to regenerate bone, cartilage, myelosupportive stroma, marrow adipocytes) and in the chondrogenic and osteogenic lineage progeny where collagenolytic activity is a requisite for proper cell and tissue function Udgivelsesdato: 2009/11
- Type:
- Journal article
- Language:
- English
- Published in:
- Journal of Bone and Mineral Research, 2009, Vol 24, Issue 11, p. 1905-1916
- Keywords:
- Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Adipocytes; Animals; Body Weight; Bone Marrow; Bone and Bones; Cartilage; Cell Lineage; Cell Proliferation; Chondrocytes; Collagen Type II; Matrix Metalloproteinase 14; Mice; Organ Specificity; Osteogenesis; Rats; Stem Cells; Survival Analysis; Transgenes; Weight Gain
- Main Research Area:
- Science/technology
- Publication Status:
- Published
- Review type:
- Peer Review
- Submission year:
- 2009
- Scientific Level:
- Scientific
- ID:
- 15254204
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