PMID- 17620297 OWN - NLM STAT- MEDLINE DCOM- 20071214 LR - 20161124 IS - 1097-4652 (Electronic) IS - 0021-9541 (Linking) VI - 214 IP - 1 DP - 2008 Jan TI - TRAIL inhibits osteoclastic differentiation by counteracting RANKL-dependent p27Kip1 accumulation in pre-osteoclast precursors. PG - 117-25 AB - Experimental evidences indicate that the TNF family member TNF-related apoptosis inducing ligand (TRAIL) might be involved in modulating osteoclastic differentiation. The ability of recombinant soluble TRAIL to affect bone density in vivo was evaluated by using 4-week-old mice subcutaneously (s.c.) injected with TRAIL for 8 days. TRAIL injection induced a significant increase of tibia trabecular thickness and total bone mass in 4-week-old mice, accompanied by a significant decrease of TRAP serum levels, without modulation of osteocalcin and osteoprotegerin (OPG). Parallel experiments performed in vitro showed that inhibition of osteoclastic differentiation, induced by treatment of human peripheral blood osteoclast precursors with TRAIL, was associated to inhibition of receptor activator of nuclear factor kappa B ligand (RANKL)-induced accumulation of p27(Kip1). The potential role of p27(Kip1) pathway in mediating the anti-osteoclastic activity of TRAIL was further suggested by in vitro gene knock-down experiments performed in osteoclast precursor cultures. Taken together, our data strongly suggest that recombinant TRAIL inhibits osteoclastogenesis by inducing the ubiquitin-mediated degradation of p27(Kip1). CI - (c) 2007 Wiley-Liss, Inc. FAU - Zauli, Giorgio AU - Zauli G AD - Department of Biomedicine, University of Trieste, Trieste, Italy. zauli@units.it FAU - Rimondi, Erika AU - Rimondi E FAU - Stea, Susanna AU - Stea S FAU - Baruffaldi, Fabio AU - Baruffaldi F FAU - Stebel, Marco AU - Stebel M FAU - Zerbinati, Carlotta AU - Zerbinati C FAU - Corallini, Federica AU - Corallini F FAU - Secchiero, Paola AU - Secchiero P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - J Cell Physiol JT - Journal of cellular physiology JID - 0050222 RN - 0 (Fluorescent Dyes) RN - 0 (Indoles) RN - 0 (Isoenzymes) RN - 0 (RANK Ligand) RN - 0 (RNA, Small Interfering) RN - 0 (Recombinant Proteins) RN - 0 (TNF-Related Apoptosis-Inducing Ligand) RN - 0 (Tnfsf10 protein, mouse) RN - 0 (Tnfsf11 protein, mouse) RN - 104982-03-8 (Osteocalcin) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 47165-04-8 (DAPI) RN - EC 3.1.3.2 (Acid Phosphatase) RN - EC 3.1.3.2 (Acp5 protein, mouse) RN - EC 3.1.3.2 (Tartrate-Resistant Acid Phosphatase) RN - EC 3.4.- (Cathepsins) RN - EC 3.4.22.38 (CTSK protein, human) RN - EC 3.4.22.38 (Cathepsin K) RN - EC 3.4.22.38 (Ctsk protein, mouse) SB - IM MH - Acid Phosphatase/analysis/immunology MH - Animals MH - Cathepsin K MH - Cathepsins/analysis/metabolism MH - Cell Differentiation/*drug effects MH - Cell Nucleus/metabolism MH - Cell Separation/methods MH - Cells, Cultured MH - Cyclin-Dependent Kinase Inhibitor p27/*biosynthesis MH - Drug Administration Schedule MH - Enzyme-Linked Immunosorbent Assay MH - Fluorescent Dyes MH - Humans MH - Indoles MH - Injections, Subcutaneous MH - Isoenzymes/analysis/immunology MH - Leukocytes, Mononuclear/cytology/*metabolism MH - Mice MH - Osteocalcin/analysis MH - Osteoclasts/*drug effects/physiology MH - RANK Ligand/*metabolism MH - RNA, Small Interfering/metabolism MH - Recombinant Proteins/administration & dosage/pharmacology MH - Solubility MH - TNF-Related Apoptosis-Inducing Ligand/administration & dosage/genetics/*pharmacology MH - Tartrate-Resistant Acid Phosphatase EDAT- 2007/07/11 09:00 MHDA- 2007/12/15 09:00 CRDT- 2007/07/11 09:00 PHST- 2007/07/11 09:00 [pubmed] PHST- 2007/12/15 09:00 [medline] PHST- 2007/07/11 09:00 [entrez] AID - 10.1002/jcp.21165 [doi] PST - ppublish SO - J Cell Physiol. 2008 Jan;214(1):117-25. doi: 10.1002/jcp.21165.