The Role of Mast Cells in Parathyroid Bone Disease
| Autor: | Jean D. Sibonga, Russell T. Turner, Kevin Marley, Urszula T. Iwaniec |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Bone disease Endocrinology Diabetes and Metabolism Osteitis fibrosa cystica Osteitis Fibrosa Cystica Parathyroid hormone PI3K Piperazines Bone remodeling hyperparathyroidism Rats Sprague-Dawley Mice 0302 clinical medicine stem cell factor Bone Marrow Orthopedics and Sports Medicine Mast Cells Child Phosphoinositide-3 Kinase Inhibitors Aged 80 and over Platelet-Derived Growth Factor 0303 health sciences PDGF Middle Aged 3. Good health Trapidil Proto-Oncogene Proteins c-kit medicine.anatomical_structure Parathyroid Hormone Child Preschool Benzamides Imatinib Mesylate Original Article Female Wortmannin Adult medicine.medical_specialty Adolescent 030209 endocrinology & metabolism Bone resorption Metabolic bone disease 03 medical and health sciences Internal medicine medicine Animals Humans 030304 developmental biology Aged Parathyroid hormone-related protein iliac crest bone biopsy business.industry Parathyroid Hormone-Related Protein medicine.disease Rats Androstadienes Bone Diseases Metabolic Endocrinology Pyrimidines Bone marrow business |
| Zdroj: | Journal of Bone and Mineral Research |
| ISSN: | 1523-4681 0884-0431 |
| Popis: | Chronic hyperparathyroidism (HPT) is a common cause of metabolic bone disease. These studies investigated the underlying cellular and molecular mechanisms responsible for the detrimental actions of elevated parathyroid hormone (PTH) on the skeleton. Bone biopsies from hyperparathyroid patients revealed an association between parathyroid bone disease and increased numbers of bone marrow mast cells. We therefore evaluated the role of mast cells in the etiology of parathyroid bone disease in a rat model for chronic HPT. In rats, mature mast cells were preferentially located at sites undergoing bone turnover, and the number of mast cells at the bone–bone marrow interface was greatly increased following treatment with PTH. Time-course studies and studies employing parathyroid hormone–related peptide (PTHrP), as well as inhibitors of platelet-derived growth factor-A (PDGF-A, trapidil), kit (gleevec), and PI3K (wortmannin) signaling revealed that mature mast cell redistribution from bone marrow to bone surfaces precedes and is associated with osteitis fibrosa, a hallmark of parathyroid bone disease. Importantly, mature mast cells were not observed in the bone marrow of mice. Mice, in turn, were resistant to the development of PTH-induced bone marrow fibrosis. These findings suggest that the mast cell may be a novel target for treatment of metabolic bone disease. © 2010 American Society for Bone and Mineral Research. |
| Databáze: | OpenAIRE |
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