Damaged articular cartilage rarely heals or regenerates in middle-aged and elderly adults, suggesting that the chondrogenic potential of mesenchymal stem cells declines with age. To test this hypothesis, we measured the responses of rat bone marrow-derived mesenchymal stem cells (BMSCs) to chondrogenic induction in vitro. BMSCs from immature rats (1 week old), young adult rats (12 weeks old), and old adult rats (1 year old) were analyzed for cartilage extracellular matrix (ECM) production. Histologic analysis showed strong cartilage ECM formation by BMSCs from 1-week-old rats, but not by BMSCs from 12-week-old or 1-year-old rats. Real-time polymerase chain reaction revealed age-related declines in messenger RNA encoding type II collagen, aggrecan, and link protein, three major cartilage ECM components. Microarray analysis indicated significant age-related differences in the expression of genes that influence cartilage ECM formation. These findings support the hypothesis that the chondrogenic potential of mesenchymal stem cells declines with age.
机构:
Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Pai, M.
Helmy, S.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Helmy, S.
Jiao, L. R.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Jiao, L. R.
Levicar, N.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Levicar, N.
Tait, P.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Tait, P.
Marley, S. B.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Marley, S. B.
Thillainayagam, A.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Thillainayagam, A.
Bansi, D.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Bansi, D.
Nicholls, J. P.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Nicholls, J. P.
Jensen, S.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Jensen, S.
Gordon, M. Y.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Gordon, M. Y.
Habib, N. A.
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Univ London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Hepatol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Haematol, London SW7 2AZ, England
Univ London Imperial Coll Sci Technol & Med, Dept Radiol, London SW7 2AZ, EnglandUniv London Imperial Coll Sci Technol & Med, Dept Surg, London SW7 2AZ, England
机构:
Tufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USATufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USA
Cho, Hyun-Jai
Lee, Juyong
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Tufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USATufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USA
Lee, Juyong
Wecker, Andrea
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Tufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USATufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USA
Wecker, Andrea
Yoon, Young-sup
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Tufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USATufts Univ, Sch Med, Div Cardiovasc Res, Caritas St Elizabeths Med Ctr, Brighton, MA 02135 USA