title: Differential load-regulated global gene expression in mouse trabecular osteocytes.
abstract: Osteocytes are considered the skeletal mechanosensors. However, because osteocytes, particularly trabecular, are barely accessible to in vivo molecular analyses, very little is known on the signals transmitted by these cells to the extra-trabecular milieu. To investigate so called "osteocytic genes" involved in extracellular signaling, we have used a recently developed model whereby a single caudal mouse vertebra (C5) is subjected to controlled compression loading and further devised a method for the isolation of high quality RNA from trabecular osteocytes. RNA samples from loaded and sham-loaded individual vertebrae where then subjected to gene array analysis following the administration of a single or repetitive loading doses (thrice weekly for 4 weeks). Focusing on extracellular genes potentially involved in mediating osteocyte-derived signals to the trabecular surface, we identified sets of genes differentially regulated by either single or multiple loading bouts as well as genes affected by both loading protocols. A comparison with published studies on load-regulated genes in cortical osteocytes revealed that the majority of these genes are specifically activated/silenced in the trabecular bone. Many of these genes could be clustered according to processes directly relevant to the life cycle and activity of osteoblasts and osteoclasts and their progenitors. The present findings are consistent with an osteocytic role in the control of trabecular bone remodeling and mass and provide a comprehensive database of load-regulated genes in trabecular osteocytes that is potentially useful in further mouse genetic studies and identification of drug targets to combat osteoporosis.
authors.affiliation: Institute for Biomechanics, ETH Zürich, Wolfgang-Pauli-Strasse 10, 8093 Zurich, Switzerland. eladw@ekmd.huji.ac.il
authors.forename: Elad
authors.initials: E
authors.lastname: Wasserman
authors.forename: Duncan
authors.initials: D
authors.lastname: Webster
authors.forename: Gisela
authors.initials: G
authors.lastname: Kuhn
authors.forename: Malka
authors.initials: M
authors.lastname: Attar-Namdar
authors.forename: Ralph
authors.initials: R
authors.lastname: Müller
authors.forename: Itai
authors.initials: I
authors.lastname: Bab
mesh_terms: D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism*; D017931:DNA Primers; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D051379:Mice; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010011:Osteocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger