title: Molecular profile of catabolic versus anabolic treatment regimens of parathyroid hormone (PTH) in rat bone: an analysis by DNA microarray.
abstract: Teriparatide, human PTH (1-34), a new therapy for osteoporosis, elicits markedly different skeletal responses depending on the treatment regimen. In order to understand potential mechanisms for this dichotomy, the present investigation utilized microarrays to delineate the genes and pathways that are regulated by intermittent (subcutaneous injection of 80 microg/kg/day) and continuous (subcutaneous infusion of 40 microg/kg/day by osmotic mini pump) PTH (1-34) for 1 week in 6-month-old female rats. The effect of each PTH regimen was confirmed by histomorphometric analysis of the proximal tibial metaphysis, and mRNA from the distal femoral metaphysis was analyzed using an Affymetrix microarray. Both PTH paradigms co-regulated 22 genes including known bone formation genes (i.e., collagens, osteocalcin, decorin, and osteonectin) and also uniquely modulated additional genes. Intermittent PTH regulated 19 additional genes while continuous treatment regulated 173 additional genes. This investigation details for the first time the broad profiling of the gene and pathway changes that occur in vivo following treatment of intermittent versus continuous PTH (1-34). These results extend previous observations of gene expression changes and reveal the in vivo regulation of BMP3 and multiple neuronal genes by PTH treatment.
authors.affiliation: Integrative Biology, Lilly Research Labs, Indianapolis, Indiana 46285, USA.
authors.forename: Jude E
authors.initials: JE
authors.lastname: Onyia
authors.forename: Leah M
authors.initials: LM
authors.lastname: Helvering
authors.forename: Lawrence
authors.initials: L
authors.lastname: Gelbert
authors.forename: Tao
authors.initials: T
authors.lastname: Wei
authors.forename: Shuguang
authors.initials: S
authors.lastname: Huang
authors.forename: Peining
authors.initials: P
authors.lastname: Chen
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Dow
authors.forename: Avudaiappan
authors.initials: A
authors.lastname: Maran
authors.forename: Minzhi
authors.initials: M
authors.lastname: Zhang
authors.forename: Sutada
authors.initials: S
authors.lastname: Lotinun
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.forename: David L
authors.initials: DL
authors.lastname: Halladay
authors.forename: Rebecca R
authors.initials: RR
authors.lastname: Miles
authors.forename: Nalini H
authors.initials: NH
authors.lastname: Kulkarni
authors.forename: Emily M
authors.initials: EM
authors.lastname: Ambrose
authors.forename: Yanfei L
authors.initials: YL
authors.lastname: Ma
authors.forename: Charles A
authors.initials: CA
authors.lastname: Frolik
authors.forename: Masahiko
authors.initials: M
authors.lastname: Sato
authors.forename: Henry U
authors.initials: HU
authors.lastname: Bryant
authors.forename: Russell T
authors.initials: RT
authors.lastname: Turner
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D005260:Female; D020869:Gene Expression Profiling; D009474:Neurons / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats
chemical_list: D010281:Parathyroid Hormone; D010446:Peptide Fragments