Src Inhibitor Reduces Permeability Without Disturbing Vascularization and Prevents Bone Destruction in Steroid-associated Osteonecrotic Lesions in Rabbits
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To examine the therapeutic effect of Src inhibitor on the VEGF mediating vascular hyperpermeability and bone destruction within steroid-associated osteonecrotic lesions in rabbits. Rabbits with high risk for progress to destructive repair in steroid-associated osteonecrosis were selected according to our published protocol. The selected rabbits were systemically administrated with either Anti-VEGF antibody (Anti-VEGF Group) or Src inhibitor (Src-Inhibition Group) or VEGF (VEGF-Supplement Group) or a combination of VEGF and Src inhibitor (Supplement &Inhibition Group) or control vehicle (Control Group) for 4 weeks. At 0, 2 and 4 weeks after administration, in vivo dynamic MRI, micro-CT based-angiography, histomorphometry and immunoblotting were employed to evaluate the vascular and skeletal events in different groups. The incidence of the destructive repair in the Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group was all significantly lower than that in the Control Group. The angiogenesis was promoted in VEGF-Supplement Group, Src-Inhibition Group and Supplement &Inhibition Group, while the hyperpermeability was inhibited in Anti-VEGF Group, Src-Inhibition Group and Supplement &Inhibition Group. The trabecular structure was improved in Src-Inhibition Group and Supplement &Inhibition Group. Src inhibitor could reduce permeability without disturbing vascularization and prevent destructive repair in steroid-associated osteonecrosis.
Liu C, Liu N, Zhang S, Ma G, Yang H, Kong L Acta Pharmacol Sin. 2020; 42(3):370-381.
PMID: 33303991 PMC: 8027612. DOI: 10.1038/s41401-020-00568-2.
Fratzl-Zelman N, Roschger P, Kang H, Jha S, Roschger A, Blouin S J Bone Miner Res. 2019; 34(5):883-895.
PMID: 30667555 PMC: 8302214. DOI: 10.1002/jbmr.3656.
The Janus Face of VEGF in Stroke.
Geiseler S, Morland C Int J Mol Sci. 2018; 19(5).
PMID: 29734653 PMC: 5983623. DOI: 10.3390/ijms19051362.
Gao F, Sabbineni H, Artham S, Somanath P J Cell Physiol. 2017; 232(10):2599-2609.
PMID: 28075016 PMC: 5482788. DOI: 10.1002/jcp.25791.
Guo H, Zhou H, Lu J, Qu Y, Yu D, Tong Y Neural Regen Res. 2016; 11(1):174-9.
PMID: 26981109 PMC: 4774214. DOI: 10.4103/1673-5374.175067.