Mutation in Osteoactivin Promotes Receptor Activator of NFkappaB Ligand (RANKL)-mediated Osteoclast Differentiation and Survival but Inhibits Osteoclast Function.
*Mutation; Akt; Animals; bone; bone marrow; Bone Remodeling; Cell Differentiation/*physiology; Cell Survival/*physiology; Eye Proteins/*genetics; Inbred DBA; MAP kinases (MAPKs); Membrane Glycoproteins/*genetics; Mice; osteoactivin; osteoclast; Osteoclasts/*cytology; osteopetrosis; RANK Ligand/metabolism/*physiology; Signal Transduction; X-Ray Microtomography
We previously reported on the importance of osteoactivin (OA/Gpnmb) in osteogenesis. In this study, we examined the role of OA in osteoclastogenesis, using mice with a nonsense mutation in the Gpnmb gene (D2J) and wild-type controls (D2J/Gpnmb(+)). In these D2J mice, micro-computed tomography and histomorphometric analyses revealed increased cortical thickness, whereas total porosity and eroded surface were significantly reduced in D2J mice compared with wild-type controls, and these results were corroborated by lower serum levels of
Abdelmagid Samir M; Sondag Gregory R; Moussa Fouad M; Belcher Joyce Y; Yu Bing; Stinnett Hilary; Novak Kimberly; Mbimba Thomas; Khol Matthew; Hankenson Kurt D; Malcuit Christopher; Safadi Fayez F
The Journal of biological chemistry
2015
2015-08
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1074/jbc.M114.624270" target="_blank" rel="noreferrer noopener">10.1074/jbc.M114.624270</a>
Transgenic Expression of Osteoactivin/gpnmb Enhances Bone Formation In Vivo and Osteoprogenitor Differentiation Ex Vivo.
Animals; Bone and Bones/*metabolism; Bone Density/physiology; Bone Remodeling/genetics/*physiology; Bone Resorption/metabolism; Cell Differentiation/genetics/*physiology; Eye Proteins/genetics/*metabolism; Membrane Glycoproteins/genetics/*metabolism; Mice; Osteoblasts/*cytology; Osteoclasts/*cytology; Osteogenesis/genetics; Protein-Serine-Threonine Kinases/metabolism; Receptor; Receptors; Transforming Growth Factor beta/metabolism; Transforming Growth Factor-beta Type I; Transgenic
Initial identification of osteoactivin (OA)/glycoprotein non-melanoma clone B (gpnmb) was demonstrated in an osteopetrotic rat model, where OA expression was increased threefold in mutant bones, compared to normal. OA mRNA and protein expression increase during active bone regeneration post-fracture, and primary rat osteoblasts show increased OA expression during differentiation in vitro. To further examine OA/gpnmb as an osteoinductive agent, we characterized the skeletal phenotype of transgenic mouse overexpressing OA/gpnmb under the
Frara Nagat; Abdelmagid Samir M; Sondag Gregory R; Moussa Fouad M; Yingling Vanessa R; Owen Thomas A; Popoff Steven N; Barbe Mary F; Safadi Fayez F
Journal of cellular physiology
2016
2016-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1002/jcp.25020" target="_blank" rel="noreferrer noopener">10.1002/jcp.25020</a>