PMID- 30803152
OWN - NLM
STAT- MEDLINE
DCOM- 20200527
LR  - 20200527
IS  - 1932-7005 (Electronic)
IS  - 1932-6254 (Print)
IS  - 1932-6254 (Linking)
VI  - 13
IP  - 5
DP  - 2019 May
TI  - Nanoparticulate mineralized collagen glycosaminoglycan materials directly and 
      indirectly inhibit osteoclastogenesis and osteoclast activation.
PG  - 823-834
LID - 10.1002/term.2834 [doi]
AB  - The ability of the extracellular matrix (ECM) to direct cell fate has generated 
      the potential for developing a materials-only strategy for tissue regeneration. 
      Previously, we described a nanoparticulate mineralized collagen glycosaminoglycan 
      (MC-GAG) material that efficiently induced osteogenic differentiation of human 
      mesenchymal stem cells (hMSCs) and calvarial bone healing without exogenous 
      growth factors or progenitor cell expansion. In this work, we evaluated the 
      interactions between MC-GAG and primary human osteoclasts (hOCs). In the absence 
      of hMSCs, mineralized Col-GAG materials directly inhibited hOC viability, 
      proliferation, and resorption in contrast to nonmineralized Col-GAG, which 
      demonstrated a modest inhibition of resorptive activity only. Cocultures 
      containing differentiating hMSCs with hOCs demonstrated increased hOC-mediated 
      resorption only on Col-GAG while MC-GAG cocultures continued to inhibit 
      resorption. Unlike Col-GAG, hMSCs on MC-GAG expressed increased amounts of 
      osteoprotegerin (OPG) protein, the major endogenous osteoclast inhibitor. 
      Interestingly, OPG expression was found to be antagonized by small mothers 
      against decapentaplegic1/5 (Smad1/5) phosphorylation, an obligate pathway for 
      osteogenic differentiation of hMSCs on MC-GAG, and potentiated by extracellular 
      signal-regulated kinase (ERK1/2) phosphorylation. Collectively, these results 
      suggested that the MC-GAG material both directly inhibited the osteoclast 
      viability, proliferation, and resorptive activity as well as induced hMSCs to 
      secrete osteoprotegerin, an antiosteoclastogenic factor, via a signalling pathway 
      distinct from osteogenic differentiation.
CI  - (c) 2019 John Wiley & Sons, Ltd.
FAU - Ren, Xiaoyan
AU  - Ren X
AD  - Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of 
      Medicine, Los Angeles, California.
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
AD  - UCLA Molecular Biology Institute, Los Angeles, California.
FAU - Zhou, Qi
AU  - Zhou Q
AD  - Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of 
      Medicine, Los Angeles, California.
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
AD  - UCLA Molecular Biology Institute, Los Angeles, California.
FAU - Foulad, David
AU  - Foulad D
AD  - Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of 
      Medicine, Los Angeles, California.
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
AD  - UCLA Molecular Biology Institute, Los Angeles, California.
FAU - Dewey, Marley J
AU  - Dewey MJ
AD  - Department of Materials Science and Engineering, Institute for Genomic Biology, 
      University of Illinois at Urbana-Champaign, Urbana, Illinois.
FAU - Bischoff, David
AU  - Bischoff D
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
FAU - Miller, Timothy A
AU  - Miller TA
AD  - Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of 
      Medicine, Los Angeles, California.
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
FAU - Yamaguchi, Dean T
AU  - Yamaguchi DT
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
FAU - Harley, Brendan A C
AU  - Harley BAC
AD  - Department of Chemical and Biomolecular Engineering, Institute for Genomic 
      Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois.
FAU - Lee, Justine C
AU  - Lee JC
AUID- ORCID: 0000-0002-8943-0837
AD  - Division of Plastic and Reconstructive Surgery, UCLA David Geffen School of 
      Medicine, Los Angeles, California.
AD  - Research Service, Greater Los Angeles VA Healthcare System, Los Angeles, 
      California.
AD  - UCLA Molecular Biology Institute, Los Angeles, California.
LA  - eng
GR  - IK2 BX002442/BX/BLRD VA/United States
GR  - R21 AR063331/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190415
PL  - England
TA  - J Tissue Eng Regen Med
JT  - Journal of tissue engineering and regenerative medicine
JID - 101308490
RN  - 0 (Glycosaminoglycans)
RN  - 0 (glucosaminoglycans)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - *Cell Differentiation
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Collagen/*chemistry
MH  - Glycosaminoglycans/*chemistry
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Nanoparticles/*chemistry
MH  - Osteoclasts/cytology/*metabolism
PMC - PMC6529242
MID - NIHMS1014033
OTO - NOTNLM
OT  - bone regeneration
OT  - bone resorption
OT  - collagen glycosaminoglycan
OT  - nanoparticle
OT  - osteoclast
OT  - osteoprotegerin
COIS- Conflict of Interest Statement: There are no conflicts of interest to declare 
      among any of the authors.
EDAT- 2019/02/26 06:00
MHDA- 2020/05/28 06:00
PMCR- 2020/05/01
CRDT- 2019/02/26 06:00
PHST- 2018/08/01 00:00 [received]
PHST- 2018/11/20 00:00 [revised]
PHST- 2019/02/13 00:00 [accepted]
PHST- 2019/02/26 06:00 [pubmed]
PHST- 2020/05/28 06:00 [medline]
PHST- 2019/02/26 06:00 [entrez]
PHST- 2020/05/01 00:00 [pmc-release]
AID - 10.1002/term.2834 [doi]
PST - ppublish
SO  - J Tissue Eng Regen Med. 2019 May;13(5):823-834. doi: 10.1002/term.2834. Epub 2019 
      Apr 15.