Immunosuppression with FK506 Increases Bone Induction in Demineralized Isogeneic and Xenogeneic Bone Matrix in the Rat

作者: Gregor Voggenreiter , Stefan Assenmacher , Ernst Kreuzfelder , Markus Wolf , Mi‐Ran Kim

DOI: 10.1359/JBMR.2000.15.9.1825

关键词:

摘要: The aim of the present study was to investigate a systemic induction bone formation in rats by immunosuppression with FK506 (1 mg/kg body weight intraperitoneally [ip]) model osteoinduction isogeneic and xenogeneic demineralized matrix (DBM) for period 28 days. In particular, alterations vitro cytokine synthesis changes lymphocyte subsets were studied. DBM implanted intramuscularly abdominal wall Lewis (seven per group). Blood sampled on days −7, 0, 7, determination tumor necrosis factor α (TNF-α) flow cytometry (CD3+, CD4+, CD8+, CD45+, ED9+, Ia+ antibodies). Ossicles de novo formed tibias removed day after double tetracycline labeling histomorphometric analysis. Immunosuppression significantly decreased lipopolysaccharide (LPS)-stimulated 7 (p < 0.05). Compared control animals treatment increased volume induced (2.1 ± 0.3 mm3 vs. 10.8 0.9 mm3) (0 4.7 0.8 DBM. Bone histomorphometry revealed that both resorption, accompanied significant reduction relative trabecular area (Tb.Ar). caused decrease counts CD8+ T cells probably because destruction or dislocation these cells. This suggests amount degree cell activation terms mean fluorescence intensity (MFI) may be associated metabolism. support this, statistical analysis positive correlation between parameters as well resorption CD4+/CD8+ ratio. There negative remodeling metaphysis tibia (BV), respectively, MFI values CD3+/Ia+ These findings suggest an important role lymphocytes vivo. marked increase However, conclusion increases fracture healing warrants further investigation.

参考文章(46)
M. H. M. Wauben, C. P. M. Broeren, P. J. S. Van Kooten, M. Van Meurs, W. Van Eden, E. Claassen, M. A. Lucassen, C. J. P. Boog, Activated rat T cells synthesize and express functional major histocompatibility class II antigens. Immunology. ,vol. 84, pp. 193- 201 ,(1995)
Bruce G. Gold, Toni Storm-Dickerson, Daniel R. Austin, The immunosuppressant FK506 increases functional recovery and nerve regeneration following peripheral nerve injury Restorative Neurology and Neuroscience. ,vol. 6, pp. 287- 296 ,(1994) , 10.3233/RNN-1994-6404
BG Gold, K Katoh, T Storm-Dickerson, The immunosuppressant FK506 increases the rate of axonal regeneration in rat sciatic nerve The Journal of Neuroscience. ,vol. 15, pp. 7509- 7516 ,(1995) , 10.1523/JNEUROSCI.15-11-07509.1995
S M Bidner, I M Rubins, J V Desjardins, D J Zukor, D Goltzman, Evidence for a humoral mechanism for enhanced osteogenesis after head injury. Journal of Bone and Joint Surgery, American Volume. ,vol. 72, pp. 1144- 1149 ,(1990) , 10.2106/00004623-199072080-00004
M. R. Urist, Bone: Formation by Autoinduction Science. ,vol. 150, pp. 893- 899 ,(1965) , 10.1126/SCIENCE.150.3698.893
Mark C. Horowitz, Gary E. Friedlaender, He-Ying Qian, The immune response: the efferent arm. Clinical Orthopaedics and Related Research. ,vol. 326, pp. 25- 34 ,(1996) , 10.1097/00003086-199605000-00004
Anders L. Ekelund, Olle Nilsson, Effects of cyclosporin A on bone turnover and on resorption of demineralized bone matrix. Clinical Orthopaedics and Related Research. ,vol. 326, pp. 127- 134 ,(1996) , 10.1097/00003086-199605000-00015
A. W. Thomson, C. A. Bonham, A. Zeevi, Mode of action of tacrolimus (FK506): molecular and cellular mechanisms. Therapeutic Drug Monitoring. ,vol. 17, pp. 584- 591 ,(1995) , 10.1097/00007691-199512000-00007