New insights into the regulation of cathepsin K gene expression by osteoprotegerin ligand.
Cathepsin K plays a key role in bone resorption. We provide the first evidence that osteoprotegerin ligand (OPGL), a critical pro-resorptive cytokine, acutely stimulates the expression of cathepsin K in osteoclasts. We used in situ RT-PCR and real time quantitative RT-PCR to analyze cathepsin K gene expression. OPGL enhanced cathepsin K mRNA levels in mature osteoclasts isolated from rat neonatal long bones. OPGL together with macrophage colony-stimulating factor (M-CSF) also stimulated cathepsin K gene expression in monocytic cells and multinucleate osteoclasts in bone marrow cultures. Real time quantitative RT-PCR demonstrated high levels of cathepsin K mRNA in bone marrow cultures, paralleling the degree of osteoclastogenesis. We therefore suggest that OPGL enhances bone resorption, at least in part, by inducing cathepsin K gene expression.
Corisdeo
S
S
Geriatric Research Education and Clinical Center, Bronx VA Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468, USA.
Gyda
M
M
Zaidi
M
M
Moonga
B S
BS
Troen
B R
BR
D000818:Animals; D000831:Animals, Newborn; D001854:Bone Marrow Cells / Q000166:cytology; D002117:Calcitriol / Q000494:pharmacology; D002352:Carrier Proteins / Q000494:pharmacology*; D056657:Cathepsin K; D002403:Cathepsins / Q000235:genetics*; D018929:Cell Culture Techniques / Q000379:methods; D002467:Cell Nucleus / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D005269:Femur; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013977:Tibia; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects*
D002352:Carrier Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016173:Macrophage Colony-Stimulating Factor; D002403:Cathepsins; D056657:Cathepsin K; C534133:Ctsk protein, rat; D002117:Calcitriol