Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2

OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model.METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry.RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg.CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

Activin A/BMP2 Chimera (AB204) Exhibits Better Spinal Bone Fusion Properties than rhBMP2

OBJECTIVE: To compare the spinal bone fusion properties of activin A/BMP2 chimera (AB204) with recombinant human bone morphogenetic protein (rhBMP2) using a rat posterolateral spinal fusion model. METHODS: The study was designed to compare the effects and property at different dosages of AB204 and rhBMP2 on spinal bone fusion. Sixty-one male Sprague-Dawley rats underwent posterolateral lumbar spinal fusion using one of nine treatments during the study, that is, sham; osteon only; 3.0 μg, 6.0 μg, or 10.0 μg of rhBMP2 with osteon; and 1.0 μg, 3.0 μg, 6.0 μg, or 10.0 μg of AB204 with osteon. The effects and property on spinal bone fusion was calculated at 4 and 8 weeks after treatment using the scores of physical palpation, simple radiograph, micro-computed tomography, and immunohistochemistry. RESULTS: Bone fusion scores were significantly higher for 10.0 μg AB204 and 10.0 μg rhBMP2 than for osteon only or 1.0 μg AB204. AB204 exhibited more prolonged osteoblastic activity than rhBMP2. Bone fusion properties of AB204 were similar with the properties of rhBMP2 at doses of 6.0 and 10.0 μg, but, the properties of AB204 at doses of 3.0 μg exhibited better than the properties of rhBMP2 at doses of 3.0 μg. CONCLUSION: AB204 chimeras could to be more potent for treating spinal bone fusion than rhBMP2 substitutes with increased osteoblastic activity for over a longer period.

Interleukin-7 Receptor is Indispensable for Proliferation and Survival in Thymic gamma sigma T Cell Development

BACKGROUND: Interleukin-7 receptor (IL-7R) alpha-deficient mice have small numbers of B cells and alpha beta T cells in periphery, they totally lack gamma sigma T cells. In addition, the V-J recombination and transcription of TCRgamma genes is also severely impaired in IL-7Ralpha-deficient mice. Stat5, a signaling molecule of the IL-7R, induces germline transcription in the TCRgamma locus, and promotes V-J recombination and gamma sigma T cell development. However, the roles for IL-7R signaling pathway in thymic or extrathymic gamma sigma T cell development are largely unknown. METHODS: To clarify the role of the IL-7 receptor in proliferation and survival of gamma sigma T cells, we introduced the TCR gamma sigma transgene, Vgamma2/ Vsigma5, into IL-7Ralpha-deficient mice, and investigated the development of gamma sigma T cells. RESULTS: We found that Vgamma2/Vsigma5 transgene restored gamma sigma T cells in the epithelium of the small intestine (IEL) but not in the thymus and the spleen. Further addition of a bcl-2 transgene resulted in partial recovery of gamma sigma T cells in the thymus and the spleen of these mice. CONCLUSION: Taken together, this study revealed that the IL-7Ralpha is indispensable for proliferation and survival mainly in thymic gamma sigma T cell development.