Anabolic Action of Parathyroid Hormone Is Skeletal Site Specific at the Tissue and Cellular Levels in Mice

• Published in: Journal of bone and mineral research Vol. 17; no. 5; pp. 808 - 816
• Main Authors: Iida‐Klein, Akiko, Zhou, Hua, Lu, Shi Shou, Levine, Lance R., Ducayen‐Knowles, Mercedes, Dempster, David W., Nieves, Jeri, Lindsay, Robert
• Format: Journal Article
• Language: English
• Published: Washington, DC John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR) 01.05.2002; American Society for Bone and Mineral Research
• Subjects: Acid Phosphatase - genetics; anabolic actions; Animals; Biological and medical sciences; Bone and Bones - drug effects; Bone and Bones - metabolism; Bone Density - drug effects; bone mineral density; Carrier Proteins - genetics; Female; Femur - drug effects; Femur - metabolism; Fundamental and applied biological sciences. Psychology; Gene Expression - drug effects; Glycoproteins - genetics; Humans; Isoenzymes - genetics; Lumbar Vertebrae - drug effects; Lumbar Vertebrae - metabolism; Membrane Glycoproteins - genetics; Mice; Mice, Inbred C57BL; mouse; Osteocalcin - genetics; Osteoprotegerin; parathyroid hormone; Parathyroid Hormone - pharmacology; Peptide Fragments - pharmacology; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Calcitonin - genetics; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Tumor Necrosis Factor; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; skeletal site specificity; Skeleton and joints; Tartrate-Resistant Acid Phosphatase; Tibia - drug effects; Tibia - metabolism; Tissue Distribution; Vertebrates: osteoarticular system, musculoskeletal system; Rodentia; Tissue specificity; Density; Inorganic element; Biological activity; Osteoarticular system; Vertebrata; Mammalia; Mouse; Parathyroid hormone; Animal; Skeleton; Bone; Anabolic agent
• ISSN: 0884-0431; 1523-4681
• DOI: 10.1359/jbmr.2002.17.5.808

The cellular and molecular events triggering the anabolic response of the skeleton to exogenous parathyroid hormone (PTH) are not well understood. Despite the numerous bone mass studies in rats, few data are available for mice. Therefore, we treated 10‐week‐old female intact C57BL/6J mice with human PTH(1‐34) delivered subcutaneously at a dose of 40 μg/kg per day 5 days a week for 3 weeks and 7 weeks. Bone mineral density (BMD) of total bone, femur, tibia, and lumbar vertebrae was measured weekly by PIXImus. Bone turnover was examined by histomorphometry, and gene expression of bone formation and resorption markers and osteoclastogenesis regulators in the excised femur and tibia was assessed by reverse‐transcription polymerase chain reaction (RT‐PCR) at 3 weeks and 7 weeks. The PTH‐stimulated increase in BMD was more prominent in the tibia and femur than in the lumbar vertebrae, with an anabolic effect detected within 1‐2 weeks and BMD continuing to increase. The appearance of a detectable PTH‐stimulated increase in BMD was slower in the lumbar vertebrae where the increase was only significant after 7 weeks of treatment. Histomorphometric analysis of the proximal tibia at both 3 weeks and 7 weeks indicated significant time‐dependent increases in trabecular area, trabecular number, trabecular and cortical widths, and osteoblast and osteoid perimeters. In the lumbar vertebrae, these stimulatory effects of PTH on trabecular area, trabecular number, and cortical width were smaller and not detected until 7 weeks. PTH‐stimulated increases in bone turnover were evident by increased gene expression of osteocalcin (OC), tartrate‐resistant acid phosphatase (TRAP), and receptor of activator nuclear factor κB (NF‐κB) ligand (RANKL) in the tibia and femur. No significant difference in gene expression was observed between the two long bone sites. In conclusion, PTH exerts an anabolic action at the tissue and cellular levels in intact mice and the magnitude and temporal pattern of this anabolic action, as assessed by densitometry and histomorphometry, are skeletal site specific.