3BP2 deficient mice are osteoporotic with impaired osteoblast and osteoclast functions
| Autor: | Marc D. Grynpas, Paul D. Simoncic, Jose La Rose, Andrew Scotter, Adeline H.M. Ng, Thomas L. Willett, Noam Levaot, Salima Janmohamed, Chiachien J. Wang, Robert Rottapel, Ernst J Reichenberger, Ioannis D. Dimitriou |
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| Rok vydání: | 2011 |
| Předmět: |
Male
musculoskeletal diseases Integrins medicine.medical_specialty Histology Physiology Endocrinology Diabetes and Metabolism Osteoporosis Osteoclasts Mice Transgenic Biology Models Biological Bone resorption Bone remodeling Mice Bone Marrow SH3BP2 Osteoclast Internal medicine Bone cell medicine Deficient mouse Animals Cell Lineage Bone Resorption Proto-Oncogene Proteins c-abl Adaptor Proteins Signal Transducing Osteoblasts Chemistry Osteoblast General Medicine medicine.disease Cell biology Endocrinology medicine.anatomical_structure Gene Expression Regulation Bone marrow Research Article |
| Zdroj: | Bone. 48:S72 |
| ISSN: | 8756-3282 |
| Popis: | A fine balance between bone resorption by osteoclasts and bone formation by osteoblasts maintains bone homeostasis. In patients with cherubism, gain-of-function mutations in 3BP2, which is encoded by SH3-domain binding protein 2 (SH3BP2), cause cystic lesions with activated osteoclasts that lead to craniofacial abnormalities. However, little is known about the function of wild-type 3BP2 in regulating bone homeostasis. Here we have shown that 3BP2 is required for the normal function of both osteoblasts and osteoclasts. Initial analysis showed that Sh3bp2-/-mice developed osteoporosis as a result of reduced bone formation despite the fact that bone resorption was impaired. We demonstrated using reciprocal bone marrow chimeras, a cell-intrinsic defect of the osteoblast and osteoclast compartments in vivo. Further, Sh3bp2-/- osteoblasts failed to mature and form mineralized nodules in vitro, while Sh3bp2-/- osteoclasts spread poorly and were unable to effectively degrade dentine matrix in vitro. Finally, we showed that 3BP2 was required for Abl activation in osteoblasts and Src activation in osteoclasts, and demonstrated that the in vitro defect of each cell type was restored by the respective expression of activated forms of these kinases. These findings reveal an unanticipated role for the 3BP2 adapter protein in osteoblast function and in coordinating bone homeostatic signals in both osteoclast and osteoblast lineages. |
| Databáze: | OpenAIRE |
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