Effect of Age on Regulation of Human Osteoclast Differentiation. Issue 8 (August 2014)

• Record Type: Journal Article
• Authors: Chung, Ping‐Lin; Zhou, Shuanhu; Eslami, Behnam; Shen, Longxiang; LeBoff, Meryl S.; Glowacki, Julie
• Is Part Of: Journal of cellular biochemistry. Volume 115:Issue 8(2014:Aug.)
• Page Start: 1412
• Page End: 1419
• Publication Date: 2014-08
• Subjects: Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.24792
• Languages: English
• ISSNs: 0730-2312

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>ABSTRACT</title> <sec id="jcb24792-sec-0001" sec-type="section"> <p>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), <italic>c‐fms</italic> (r = 0.61, <italic>P</italic> = 0.006) and <italic>RANK</italic> expression (r = 0.59, <italic>P</italic> = 0.008) were increased with age (27–82 years, n = 19). In vitro generation of osteoclasts was increased with age (r = 0.89, <italic>P</italic> = 0.007). In enriched marrow stromal cells (MSCs), constitutive expression of <italic>RANKL</italic> was increased with age (r = 0.41, <italic>P</italic> = 0.049) and expression of <italic>OPG</italic> was inversely correlated with age (r = −0.43, <italic>P</italic> = 0.039). Accordingly, there was an age‐related increase in RANKL/OPG (r = 0.56, <italic>P</italic> = 0.005). These data indicate an age‐related increase in human osteoclastogenesis that is associated with an intrinsic increase in expression of <italic>c‐fms</italic> and <italic>RANK</italic> in osteoclast progenitors, and, in the supporting MSCs, an increase in pro‐osteoclastogenic <italic>RANKL</italic> expression and a decrease in anti‐osteoclastogenic <italic>OPG</italic>. 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.</p> </sec> </abstract>