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Critical Reviews™ in Eukaryotic Gene Expression
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ISSN Imprimir: 1045-4403
ISSN On-line: 2162-6502

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Critical Reviews™ in Eukaryotic Gene Expression

DOI: 10.1615/CritRevEukaryotGeneExpr.v13.i24.60
16 pages

The Effects of Colony-Stimulating Factor-1 (CSF-1) on the Development of Osteoclasts and Their Expression of Tartrate-Resistant Acid Phosphatase (TRAP) in Toothless (tl-osteopetrotic) Rats

Maria Norgard
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden
Sandy C. Marks, Jr.
Department of Cell Biology, University of Massachusetts Medical Center, Worcester 01655, USA
Finn P. Reinholt
Institute of Pathology, Rikshospitalet University Hospital, University of Oslo, Oslo, Norway
Goran Andersson
Division of Pathology, Department of Laboratory Medicine, Karolinska Institutet, Huddinge University Hospital, S-141 86 Huddinge, Sweden

RESUMO

The osteopetrotic mutation toothless (tl) in the rat is characterized by a limited number of osteoclasts with reduced amounts and/or activity of tartrate-resistant acid phosphatase (TRAP). Treatment of tl/tl mutants with the cytokine colony-stimulating factor (CSF)-1 increases both osteoclast number and enzyme activity, consistent with a loss-of-function mutation in the CSF-1 gene recently detected in this mutant. We have pursued these observations to demonstrate that there is a dose-dependent increase in osteoclast number, but not to normal levels. Osteoclasts in CSF-1–treated tl/tl mutants are large, have well-developed clear zones and ruffled borders, and secrete TRAP into resorption lacunae. The expression of TRAP mRNA, protein, and enzyme activity per bone appear normal after CSF-1 treatment. However, in contrast to the predominantly apical intracellular distribution in normal osteoclasts, an enrichment of TRAP enzyme activity in osteoclasts of CSF-1–treated tl/tl mutants is observed in the basal part of the cell. Our observations suggest that the CSF-1–treated mutant bones contain an abundance of mature osteoclasts, actively expressing markers for osteoclasts such as TRAP, cathepsin K, and matrix metalloproteinase (MMP)-9. Accumulation of TRAP at the end of the endocytic pathway in mature osteoclasts formed during CSF-1 treatment suggests that the TRAP enzyme has a rapid turnover in these highly active cells and uses a transcytotic pathway.


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