Year: 2008
Type: article
Abstract: Osteocytes, former osteoblasts buried within bone, are thought to orchestrate skeletal adaptation to mechanical stimuli. However, it remains unknown whether hormones control skeletal homeostasis through actions on osteocytes. Parathyroid hormone (PTH) stimulates bone remodeling and may cause bone loss or bone gain depending on the balance between bone resorption and formation. Herein, we demonstrate that transgenic mice expressing a constitutively active PTH receptor exclusively in osteocytes exhibit increased bone mass and bone remodeling, as well as reduced expression of the osteocyte-derived Wnt antagonist sclerostin, increased Wnt signaling, increased osteoclast and osteoblast number, and decreased osteoblast apoptosis. Deletion of the Wnt co-receptor LDL related receptor 5 (LRP5) attenuates the high bone mass phenotype but not the increase in bone remodeling induced by the transgene. These findings demonstrate that PTH receptor signaling in osteocytes increases bone mass and the rate of bone remodeling through LRP5-dependent and -independent mechanisms, respectively.
Source: PLoS ONE
Language: English
Topic: Bone Metabolism and Diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: U.S. Department of Veterans Affairs, University of Arkansas for Medical Sciences, National Institutes of Health, National Institute on Aging, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: SkyScan 1172 High-resolution desk-top micro-CT system, G1729783615, Osteocyte control of bone formation via Sost, Connexin 43 Hemichannels and Signaling In Bone, Molecular and Cellular Mechanisms of Osteoporosis, Osteocyte Control of Bone Remodeling, Lrp5 and Lrp6 signaling in bone mechanotransduction and metabolism, Microcomputed Tomography Device (Scanco UCT40)
OpenAlex ID: W2115271834