PMID- 1874190
OWN - NLM
STAT- MEDLINE
DCOM- 19910920
LR  - 20061115
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 129
IP  - 3
DP  - 1991 Sep
TI  - Two distinct effects of recombinant human tumor necrosis factor-alpha on 
      osteoclast development and subsequent resorption of mineralized matrix.
PG  - 1596-604
AB  - The multifunctional cytokine tumor necrosis factor-alpha (TNF alpha) stimulates 
      osteoclastic resorption. It is not known which steps in osteoclast formation are 
      affected by TNF alpha. We have investigated the effects of recombinant human TNF 
      alpha (rhTNF alpha) on osteoclast development and osteoclastic resorption in two 
      different in vitro resorption systems which are each characterized by a different 
      stage of development of the osteoclast. The effects were further compared to 
      those of bovine PTH-(1-84). rhTNF alpha at concentrations between 0.01-50 ng/ml 
      (3 x 10(-13) to 1.5 x 10(-9) M) did not alter the activity of mature osteoclasts, 
      measured as 45Ca release in fetal mouse radii. In the osteoclast 
      precursor-dependent system (fetal mouse metacarpals) rhTNF alpha had a biphasic 
      effect. It stimulated resorption dose-dependently from 0.01 ng/ml onward, with a 
      maximal response at 0.5 ng/ml. At concentrations above 10 ng/ml rhTNF alpha, 
      resorption was inhibited. In experiments in which irradiation was used to block 
      replication, it was found that TNF alpha stimulates the proliferation of 
      osteoclast progenitors at both low and high concentrations. As a result, at 
      relatively low concentrations, more osteoclasts were formed in the calcified 
      matrix, coinciding with an increased release of 45Ca. However, at relatively high 
      concentrations, the increase in osteoclast progenitors did not lead to increased 
      resorption, since the putative osteoclast progenitors were arrested in the 
      periosteum. In comparison, bovine PTH-(1-84) stimulated resorption independent of 
      proliferation by enhancing the differentiation of postmitotic osteoclast 
      precursors and activating mature osteoclasts. In conclusion, the effects of TNF 
      alpha on osteoclastic resorption are dependent on the stage of osteoclast 
      development and the concentrations applied.
FAU - van der Pluijm, G
AU  - van der Pluijm G
AD  - Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden, 
      The Netherlands.
FAU - Most, W
AU  - Most W
FAU - van der Wee-Pals, L
AU  - van der Wee-Pals L
FAU - de Groot, H
AU  - de Groot H
FAU - Papapoulos, S
AU  - Papapoulos S
FAU - Lowik, C
AU  - Lowik C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Parathyroid Hormone)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - *Bone Resorption
MH  - Calcification, Physiologic/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Fetus
MH  - Humans
MH  - Mice
MH  - Models, Biological
MH  - Organ Culture Techniques
MH  - Osteoclasts/cytology/drug effects/*physiology/radiation effects
MH  - Osteogenesis/*drug effects
MH  - Parathyroid Hormone/pharmacology
MH  - Recombinant Proteins/pharmacology
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 1991/09/01 00:00
MHDA- 1991/09/01 00:01
CRDT- 1991/09/01 00:00
PHST- 1991/09/01 00:00 [pubmed]
PHST- 1991/09/01 00:01 [medline]
PHST- 1991/09/01 00:00 [entrez]
AID - 10.1210/endo-129-3-1596 [doi]
PST - ppublish
SO  - Endocrinology. 1991 Sep;129(3):1596-604. doi: 10.1210/endo-129-3-1596.