title: Transient modulation of calcium and parathyroid hormone stimulates bone formation.
abstract: Intermittent administration of parathyroid hormone can stimulate bone formation. Parathyroid hormone is a natural hormone that responds to serum calcium levels. In this study, we examined whether a transient increase and/or decrease in the serum calcium can stimulate bone formation. Using a mathematical model previously developed, we first predicted the effects of administration of parathyroid hormone, neutralizing parathyroid hormone antibody, calcium, and EGTA (calcium chelator) on the serum concentration of parathyroid hormone and calcium. The model predicted that intermittent injection of parathyroid hormone and ethylene glycol tetraacetic acid transiently elevated the serum parathyroid hormone, while that of parathyroid hormone antibody and calcium transiently reduced parathyroid hormone in the serum. In vitro analysis revealed that parathyroid hormone's transient changes (both up and down) elevated activating transcription factor 4-mediated osteocalcin expression. In the mouse model of osteoporosis, both intermittent administration of calcium and ethylene glycol tetraacetic acid showed tendency to increase bone mineral density of the upper limb (ulna and humerus) and spine, but the effects varied in a region-specific manner. Collectively, the study herein supports a common bone response to administration of calcium and its chelator through their effects on parathyroid hormone.
authors: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, USA.
authors: Andy B
authors: AB
authors: Chen
authors: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA.|Department of Medical Physics & Engineering Osaka University Graduate School of Medicine Suita, Osaka, Japan.
authors: Kazumasa
authors: K
authors: Minami
authors: Department of Public Health, Medical School, New University of Lisbon, Lisbon, Portugal.
authors: João F
authors: JF
authors: Raposo
authors: Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
authors: Nariaki
authors: N
authors: Matsuura
authors: Department of Medical Physics & Engineering Osaka University Graduate School of Medicine Suita, Osaka, Japan.
authors: Masahiko
authors: M
authors: Koizumi
authors: Department of Biomedical Engineering, Indiana University Purdue University Indianapolis, Indianapolis, IN, USA. hyokota@iupui.edu.
authors: Hiroki
authors: H
authors: Yokota
authors: REQIMTE, Department of Chemistry, New University of Lisbon, Lisbon, Portugal.
authors: Hugo G
authors: HG
authors: Ferreira
mesh_terms: D000818:Animals; D015519:Bone Density / Q000502:physiology*; D002118:Calcium / Q000097:blood*; D002460:Cell Line; D006801:Humans; D051379:Mice; D008962:Models, Theoretical; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology*; D015663:Osteoporosis, Postmenopausal / Q000097:blood*; D010281:Parathyroid Hormone / Q000097:blood*
chemical_list: D010281:Parathyroid Hormone; D015675:Osteocalcin; D002118:Calcium
keywords: Bone; Calcium; EGTA; Osteoblast; Parathyroid hormone