PMID- 15138266
OWN - NLM
STAT- MEDLINE
DCOM- 20040817
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 29
DP  - 2004 Jul 16
TI  - Regulation of collagen deposition and lysyl oxidase by tumor necrosis 
      factor-alpha in osteoblasts.
PG  - 30060-5
AB  - Tumor necrosis factor-alpha (TNF-alpha) inhibits osteoblast function in vitro by 
      inhibiting collagen deposition. Studies generally support that TNF-alpha does not 
      inhibit collagen biosynthesis by osteoblasts but that collagen deposition is in 
      some way diminished. The study investigated TNF-alpha regulation of biosynthetic 
      enzymes and proteins crucial for posttranslational extracellular collagen 
      maturation in osteoblasts including procollagen C-proteinases, procollagen 
      C-proteinase enhancer, and lysyl oxidase. The working hypothesis is that such 
      regulation could inhibit collagen deposition by osteoblasts. We report that in 
      phenotypically normal MC3T3-E1 osteoblasts, TNF-alpha decreases collagen 
      deposition without decreasing collagen mRNA levels or procollagen protein 
      synthesis. Analyses of the cell layers revealed that TNF-alpha diminished the 
      levels of mature collagen cross-links, pyridinoline and deoxypyridinoline. 
      Further analyses revealed that the mRNA expression for lysyl oxidase, the 
      determining enzyme required for collagen cross-linking, is down-regulated by 
      TNF-alpha in a concentration- and time-dependent manner by up to 50%. The 
      decrease was accompanied by a significant reduction of lysyl oxidase protein 
      levels and enzyme activity. By contrast, Northern and Western blotting studies 
      revealed that procollagen C-proteinases bone morphogenic protein-1 and mammalians 
      Tolloid and procollagen C-proteinase enhancer were expressed in MC3T3-E1 cells 
      and not down-regulated. The data together demonstrate that TNF-alpha does not 
      inhibit collagen synthesis but does inhibit the expression and activity of lysyl 
      oxidase in osteoblasts, thereby contributing to perturbed collagen cross-linking 
      and accumulation. These studies identify a novel mechanism in which 
      proinflammatory cytokine modulation of an extracellular biosynthetic enzyme plays 
      a determining role in the control of collagen accumulation by osteoblasts.
FAU - Pischon, Nicole
AU  - Pischon N
AD  - Department of Oral Biology, Goldman School of Dental Medicine, Boston University, 
      Boston, Massachussetts 02118, USA.
FAU - Darbois, Laurent M
AU  - Darbois LM
FAU - Palamakumbura, Amitha H
AU  - Palamakumbura AH
FAU - Kessler, Efrat
AU  - Kessler E
FAU - Trackman, Philip C
AU  - Trackman PC
LA  - eng
GR  - DE12209/DE/NIDCR NIH HHS/United States
GR  - DE14066/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040510
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amino Acids)
RN  - 0 (Cross-Linking Reagents)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63800-01-1 (pyridinoline)
RN  - 90032-33-0 (deoxypyridinoline)
RN  - 9007-34-5 (Collagen)
RN  - EC 1.4.3.13 (Protein-Lysine 6-Oxidase)
SB  - IM
MH  - Amino Acids/pharmacology
MH  - Animals
MH  - Blotting, Northern
MH  - Blotting, Western
MH  - Cell Line
MH  - Collagen/*metabolism
MH  - Cross-Linking Reagents/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Inflammation
MH  - Mice
MH  - Osteoblasts/*metabolism
MH  - Protein Structure, Tertiary
MH  - Protein-Lysine 6-Oxidase/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2004/05/13 05:00
MHDA- 2004/08/18 05:00
CRDT- 2004/05/13 05:00
PHST- 2004/05/13 05:00 [pubmed]
PHST- 2004/08/18 05:00 [medline]
PHST- 2004/05/13 05:00 [entrez]
AID - S0021-9258(19)71016-3 [pii]
AID - 10.1074/jbc.M404208200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Jul 16;279(29):30060-5. doi: 10.1074/jbc.M404208200. Epub 2004 
      May 10.