PMID- 24700654
OWN - NLM
STAT- MEDLINE
DCOM- 20150219
LR  - 20211021
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 115
IP  - 8
DP  - 2014 Aug
TI  - Effect of age on regulation of human osteoclast differentiation.
PG  - 1412-9
LID - 10.1002/jcb.24792 [doi]
AB  - 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-kappaB 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.
CI  - (c) 2014 Wiley Periodicals, Inc.
FAU - Chung, Ping-Lin
AU  - Chung PL
AD  - Department of Orthopedic Surgery, Brigham and Women's Hospital, Harvard Medical 
      School, Boston, Massachusetts.
FAU - Zhou, Shuanhu
AU  - Zhou S
FAU - Eslami, Behnam
AU  - Eslami B
FAU - Shen, Longxiang
AU  - Shen L
FAU - LeBoff, Meryl S
AU  - LeBoff MS
FAU - Glowacki, Julie
AU  - Glowacki J
LA  - eng
GR  - R01 AG025015/AG/NIA NIH HHS/United States
GR  - R01 AG028114/AG/NIA NIH HHS/United States
GR  - AG028114/AG/NIA NIH HHS/United States
GR  - AG025015/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
RN  - 0 (TNFRSF11A protein, human)
RN  - 0 (TNFSF11 protein, human)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Aging/*metabolism/pathology
MH  - Bone Marrow Cells/metabolism
MH  - Bone Resorption/genetics/metabolism/pathology
MH  - Cell Differentiation/*genetics
MH  - Gene Expression Regulation, Developmental/*genetics
MH  - Humans
MH  - Macrophage Colony-Stimulating Factor/biosynthesis
MH  - Osteoclasts/*metabolism/pathology
MH  - Osteogenesis/genetics
MH  - Osteoprotegerin/biosynthesis
MH  - RANK Ligand/biosynthesis/metabolism
MH  - Receptor Activator of Nuclear Factor-kappa B/biosynthesis
MH  - Receptor, Macrophage Colony-Stimulating Factor/biosynthesis
MH  - Stromal Cells/metabolism
PMC - PMC4096781
MID - NIHMS596893
OTO - NOTNLM
OT  - AGING
OT  - MARROW STROMAL CELL
OT  - OPG
OT  - OSTEOCLAST
OT  - RANKL
EDAT- 2014/04/05 06:00
MHDA- 2015/02/20 06:00
PMCR- 2015/08/01
CRDT- 2014/04/05 06:00
PHST- 2014/02/14 00:00 [received]
PHST- 2014/02/19 00:00 [accepted]
PHST- 2014/04/05 06:00 [entrez]
PHST- 2014/04/05 06:00 [pubmed]
PHST- 2015/02/20 06:00 [medline]
PHST- 2015/08/01 00:00 [pmc-release]
AID - 10.1002/jcb.24792 [doi]
PST - ppublish
SO  - J Cell Biochem. 2014 Aug;115(8):1412-9. doi: 10.1002/jcb.24792.