Accelerated and increased joint damage in young mice with global inactivation of mitogen-inducible gene 6 after ligament and meniscus injury

Abstract Introduction Ligament and meniscal damage can cause joint disease. Arthritic joints contain increased amounts of epidermal growth factor receptor (EGFR) protein, and polymorphisms in EGFR are associated with arthritis risk. The role of endogenous EGFR regulation during joint disease due to ligament and meniscal trauma is unknown. Mitogen-inducible gene 6 (MIG-6) can reduce EGFR phosphorylation and downstream signaling. We examined the effect of EGFR modulation by MIG-6 on joint disease development after ligament and meniscus injury. Methods Knee ligament transection and meniscus removal were performed surgically on mice homozygous for a global inactivating mutation in MIG-6 (Mig-6 −/− ) and in wild-type (WT) animals. Results Two weeks after surgery, Mig-6 −/− mice had bone erosion as well as greater fibrous tissue area and serum RANKL concentration than WT mice. Four weeks after surgery, Mig-6 −/− mice had less cartilage and increased cell proliferation relative to contralateral control and WT knees. Increased apoptotic cells and growth outside the articulating region occurred in Mig-6 −/− mice. Tibia trabecular bone mineral density (BMD) and the number of trabeculae were lower in surgically treated knees relative to the respective control knees for both groups. BMD, as well as trabecular thickness and number, were lower in surgically treated knees from Mig-6 −/− mice relative to WT surgically treated knees. Phosphorylated EGFR staining in surgically treated knees decreased for WT mice and increased for Mig-6 −/− mice. Fewer inflammatory cells were present in the knees of WT mice. Conclusion Mig-6 −/− mice have rapid and increased joint damage after ligament and meniscal trauma. Mig-6 modification could lessen degenerative disease development after this type of injury.http://deepblue.lib.umich.edu/bitstream/2027.42/109507/1/13075_2013_Article_4169.pd

Interaction of the Fluoroquinolone Antibiotic, Ofloxacin, with Titanium Oxide Nanoparticles in Water: Adsorption and Breakdown

The mobility and fate of fluoroquinolone antibiotics in natural waters, soil-water systems and wastewater are controlled in part by surface interactions with nanometer (10(-9) m) metal oxide particles. Experiments were performed by mixing solutions of ofloxacin (OFL), a common, fluoroquinolone-class human and veterinary antibiotic, with 25 nm-TiO2 (anatase) nanoparticles at different pH conditions. Both sorption and degradation of OFL were observed in the drug-nanoparticle solutions with initial OFL concentrations of similar to 3 to 690 mu M. Though overall isotherm behavior is logarithmic, OFL removal from the solution can be approximated by linear removal coefficients (K-r). At pH 4. K-r = 42 +/- 8 L kg(-1), at pH 6 K-r = 1288 +/- 217 L kg(-1), and at pH 9 K-r = 26 +/- 7 L kg(-1). Rinsing of substrates at pH 4 resulted in desorption of approximately 11% of the original OFL removed from the solution by TiO2 nanoparticles. Less than 1% of the removed OFL at pH 6 was recovered by rinsing the substrate; and, at pH 9 about 39% of the OFL removed by nanoparticles during the initial mixing experiment was desorbed during rinsing. Mass spectral analysis of OR solutions after the removal of the solid nanoparticles yielded ions that indicate the presence of de-methylated and de-carboxylated fluoroquinolone species, resulting from the degradation of OFL at the TiO2 surface. (C) 2012 Elsevier B.V. All rights reserved