Effect of Age on Regulation of Human Osteoclast Differentiation

Authors

  • Ping-Lin Chung,

    1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Shuanhu Zhou,

    1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Behnam Eslami,

    1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Longxiang Shen,

    1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Meryl S. LeBoff,

    1. Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
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  • Julie Glowacki

    Corresponding author
    1. Department of Orthopedic Surgery, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
    2. Department of Oral and Maxillofacial Surgery, Harvard School of Dental Medicine, Boston, Massachusetts
    • Correspondence to: Julie Glowacki, Ph.D, Department of Orthopedic Surgery, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. E-mail: jglowacki@rics.bwh.harvard.edu

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ABSTRACT

Human skeletal aging is characterized as a gradual loss of bone mass due to an excess of bone resorption not balanced by new bone formation. Using human marrow cells, we tested the hypothesis that there is an age-dependent increase in osteoclastogenesis due to intrinsic changes in regulatory factors [macrophage-colony stimulating factor (M-CSF), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG)] and their receptors [c-fms and RANK]. In bone marrow cells (BMCs), c-fms (r = 0.61, P = 0.006) and RANK expression (r = 0.59, P = 0.008) were increased with age (27–82 years, n = 19). In vitro generation of osteoclasts was increased with age (r = 0.89, P = 0.007). In enriched marrow stromal cells (MSCs), constitutive expression of RANKL was increased with age (r = 0.41, P = 0.049) and expression of OPG was inversely correlated with age (r = −0.43, P = 0.039). Accordingly, there was an age-related increase in RANKL/OPG (r = 0.56, P = 0.005). These data indicate an age-related increase in human osteoclastogenesis that is associated with an intrinsic increase in expression of c-fms and RANK in osteoclast progenitors, and, in the supporting MSCs, an increase in pro-osteoclastogenic RANKL expression and a decrease in anti-osteoclastogenic OPG. These findings support the hypothesis that human marrow cells and their products can contribute to skeletal aging by increasing the generation of bone-resorbing osteoclasts. These findings help to explain underlying molecular mechanisms of progressive bone loss with advancing age in humans. J. Cell. Biochem. 115: 1412–1419, 2014. © 2014 Wiley Periodicals, Inc.

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