Loss of the PTH/PTHrP receptor along the osteoblast lineage limits the anabolic response to exercise

Autor: Siddharth Kundal, Niloufar Rostami, Joseph D. Gardinier, Chunbin Zhang, Conor S. Daly-Seiler
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Anabolism
Physiology
Organogenesis
Osteoblast lineage
Parathyroid hormone
Biochemistry
Bone remodeling
Mice
0302 clinical medicine
Animal Cells
Osteogenesis
Medicine and Health Sciences
Receptor
Musculoskeletal System
Connective Tissue Cells
Mice
Knockout
Multidisciplinary
Chemistry
medicine.anatomical_structure
Physiological Parameters
Connective Tissue
Parathyroid Hormone
Physical Sciences
Medicine
Bone Remodeling
Anatomy
Cellular Types
Research Article
medicine.medical_specialty
Science
Materials Science
Material Properties
030209 endocrinology & metabolism
PTH/PTHRP RECEPTOR
03 medical and health sciences
Internal medicine
medicine
Mechanical Properties
Animals
Tibia
Skeleton
Receptor
Parathyroid Hormone
Type 1
Osteoblasts
Bone Development
Body Weight
Parathyroid Hormone-Related Protein
Biology and Life Sciences
Cell Biology
Hormones
Biological Tissue
030104 developmental biology
Endocrinology
Cortical bone
Physiological Processes
Organism Development
Developmental Biology
Zdroj: PLoS ONE, Vol 14, Iss 1, p e0211076 (2019)
PLoS ONE
ISSN: 1932-6203
Popis: Exercise and physical activity are critical to maintain bone mass and strength throughout life. Both exercise and physical activity subject bone to a unique combination of stimuli in the forms of dynamic loading and a systemic increase in parathyroid hormone (PTH). Although dynamic loading is considered to be the primary osteogenic stimuli, the influence of increasing PTH levels remains unclear. We hypothesize that activation of the PTH/PTH-related peptide type 1 receptor (PPR) along the osteoblast lineage facilitates bone formation and improved mechanical properties in response to exercise. To test this hypothesis, conditional PPR-knockout mice (PPRcKO) were generated in which PPR expression was deleted along the osteoblast lineage under the osterix promoter. At 8-weeks of age, both PPRfl/fl and PPRcKO mice were subjected to treadmill running or sedentary conditions for 5-weeks. Under sedentary conditions, PPRcKO mice displayed significantly less bone mass as well as smaller structural-level strength (yield-load and ultimate load), while tissue level properties were largely unaffected. However, PPRcKO mice exposed to exercise displayed significantly less structural-level and tissue-level mechanical properties when compared to exercised PPRfl/fl mice. Overall, these data demonstrate that PPR expression along the osteoblast lineage is essential for exercise to improve the mechanical properties of cortical bone. Furthermore, the influence of PPR activation on material properties is unique to exercise and not during normal growth and development.
Databáze: OpenAIRE
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