Two distinct effects of recombinant human tumor necrosis factor-. alpha. on osteoclast development and subsequent resorption of mineralized matrix

Journal Article · Sun Sep 01 04:00:00 EDT 1991 · Endocrinology; (United States)

DOI:https://doi.org/10.1210/endo-129-3-1596· OSTI ID:5266453

van der Pluijm, G; Most, W; van der Wee-Pals, L; de Groot, H; Papapoulos, S; Loewik, C ^[1]

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1. Department of Endocrinology and Metabolic Diseases, University Hospital, Leiden (Netherlands)

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}. The authors 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 {times} 10(-13) to 1.5 {times} 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.

• OSTI ID: 5266453
• Journal Information: Endocrinology; (United States), Journal Name: Endocrinology; (United States) Vol. 129:3; ISSN ENDOA; ISSN 0013-7227
• Country of Publication: United States
• Language: English

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59 BASIC BIOLOGICAL SCIENCES
ALKALINE EARTH ISOTOPES
ANIMAL CELLS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BONE CELLS
CALCIUM 45
CALCIUM ISOTOPES
CELL DIFFERENTIATION
CONNECTIVE TISSUE CELLS
DAYS LIVING RADIOISOTOPES
EVEN-ODD NUCLEI
INTERMEDIATE MASS NUCLEI
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MICE
MINERALIZATION
NUCLEI
ORGANIC COMPOUNDS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SOMATIC CELLS
TRACER TECHNIQUES
VERTEBRATES