Skeletal Unloading Alleviates the Anabolic Action of Intermittent PTH(1–34) in Mouse Tibia in Association With Inhibition of PTH‐Induced Increase in c‐fos mRNA in Bone Marrow Cells

• Published in: Journal of bone and mineral research Vol. 19; no. 11; pp. 1813 - 1820
• Main Authors: Tanaka, Shinya, Sakai, Akinori, Tanaka, Masahiro, Otomo, Hajime, Okimoto, Nobukazu, Sakata, Takeshi, Nakamura, Toshitaka
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01-11-2004; American Society for Bone and Mineral Research
• Subjects: Alkaline Phosphatase - metabolism; Animals; Biological and medical sciences; Body Weight; Bone and Bones; bone marrow cells; Bone Marrow Cells - cytology; Bone Marrow Cells - metabolism; Carrier Proteins - metabolism; Cell Differentiation; c‐fos; DNA Primers - chemistry; DNA, Complementary - metabolism; Fundamental and applied biological sciences. Psychology; histomorphometry; Male; Membrane Glycoproteins - metabolism; Mice; Mice, Inbred C57BL; Osteoblasts - metabolism; Osteocalcin - metabolism; Osterix; Parathyroid Hormone - pharmacology; Peptide Fragments - pharmacology; Proto-Oncogene Proteins c-fos - metabolism; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Reverse Transcriptase Polymerase Chain Reaction; RNA - metabolism; RNA, Messenger - metabolism; Skeleton and joints; Sp7 Transcription Factor; Stem Cells; tail suspension; Tibia - drug effects; Tibia - metabolism; Time Factors; Transcription Factors - metabolism; Vertebrates: osteoarticular system, musculoskeletal system; bone marrow cells; Rodentia; c-fos; Osteoarticular system; Parathormone; histomorphometry; Vertebrata; Mammalia; tail suspension; Mouse; Parathyroid hormone; Intermittent; Tibia; Osterix; Bone marrow; Inhibition; Protooncogene; Immediate early gene
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/JBMR.040808

We analyzed the effect of unloading by tail suspension on the anabolic action of intermittent PTH in the tibia of growing mice. Unloading alleviated the PTH‐induced increase of bone formation and accelerated bone resorption, consequently reducing bone mass. Reduction of the PTH‐induced anabolic actions on bone was associated with unloading, which was apparently related to suppression of c‐fos mRNA expression in bone marrow.
Introduction: The effects of intermittent parathyroid hormone (PTH) administration on unloading bone have not been well elucidated at the cellular and molecular levels. We tested the effects of PTH on unloaded tibias of tail‐suspended mice.
Materials and Methods: Eighty male C57BL/6J mice, 8 weeks of age, were divided into four groups with loading or unloading and administration of PTH (40 μg/kg body weight) or vehicle five times per week. Mice were killed at 8 or 15 days, and both tibias were obtained. Bone histomorphometry of the trabecular bone in the proximal tibia, development of osteogenic cells, and mRNA expression of osteogenic molecules in bone marrow cells were assessed.
Results and Conclusions: At 15 days of unloading, bone volume decreased in PTH‐treated mice. The increase in the bone formation rate by PTH was depressed, and the osteoclast surface was thoroughly increased. The increase in alkaline phosphatase‐positive colony‐forming units‐fibroblastic (CFU‐f) colonies induced by PTH was maintained and that of TRACP+ multinucleated cells enhanced. The PTH‐induced increase in c‐fos mRNA was depressed, but the increases in Osterix and RANKL mRNA were maintained. Unloading promoted the PTH‐associated osteoclastogenesis and seemed to delay the progression of osteogenic differentiation in association with reduction of the PTH‐dependent increase of c‐fos mRNA in bone marrow cells.