Osteoprotegerin abrogated cortical porosity and bone marrow fibrosis in a mouse model of constitutive activation of the PTH/PTHrP receptor
| Autor: | Paul Kostenuik, Ernestina Schipani, Richa Khatri, Clare Thomas, Frank Asuncion, Riccardo Chiusaroli, Michael S. Ominsky, Masanobu Ohishi |
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| Rok vydání: | 2009 |
| Předmět: |
musculoskeletal diseases
Male medicine.medical_specialty Parathyroid hormone Osteoclasts Mice Transgenic Zoledronic Acid Bone resorption Bone and Bones Pathology and Forensic Medicine Mice Osteoprotegerin Fibrosis Osteoclast Internal medicine medicine Animals Humans Bone Resorption Receptor Parathyroid Hormone Type 1 Alendronate Diphosphonates Chemistry Hyperparathyroidism Imidazoles medicine.disease Immunohistochemistry Resorption Biomechanical Phenomena Disease Models Animal Endocrinology medicine.anatomical_structure Primary Myelofibrosis Cortical bone Bone marrow Tomography X-Ray Computed Porosity Regular Articles |
| Zdroj: | The American journal of pathology. 174(6) |
| ISSN: | 1525-2191 |
| Popis: | Intracortical porosities and marrow fibrosis are hallmarks of hyperparathyroidism and are present in bones of transgenic mice expressing constitutively active parathyroid hormone/parathyroid hormone-related protein receptors (PPR*Tg). Cortical porosity is the result of osteoclast activity; however, the etiology of marrow fibrosis is poorly understood. While osteoclast numbers and activity are regulated by osteoprotegerin (OPG), bisphosphonates suppress osteoclast activity but not osteoclast numbers. We therefore used OPG and bisphosphonates to evaluate the extent to which osteoclasts, as opposed to bone resorption, regulate marrow fibrosis in PPR*Tg mice after treatment of animals with vehicle, OPG, alendronate, or zoledronate. All three agents similarly increased trabecular bone volume in both PPR*Tg and control mice, suggesting that trabecular bone resorption was comparably suppressed by these agents. However, the number of trabecular osteoclasts was greatly decreased by OPG but not by either alendronate or zoledronate. Furthermore, intracortical porosity and marrow fibrosis were virtually abolished by OPG treatment, whereas alendronate and zoledronate only partially reduced these two parameters. The greater reductions in cortical porosity and increments in cortical bone mineral density with OPG in PPR*Tg mice were associated with greater improvements in bone strength. The differential effect of OPG versus bisphosphonates on marrow fibrosis, despite similar effects on trabecular bone volume, suggests that marrow fibrosis was related not only to bone resorption but also to the presence of osteoclasts. |
| Databáze: | OpenAIRE |
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