Osteopontin-Deficient Mice Exhibit Less Inflammation, Greater Tissue Damage, and Impaired Locomotor Recovery from Spinal Cord Injury Compared with Wild-Type Controls

Abstract

Osteopontin (OPN) is expressed in many tissues during inflammatory responses. After spinal cord injury, microglia expresses OPN at the site of injury during the early to subacute stages. However, the function of OPN in spinal cord injury is not well understood. This study examines the responses of OPN knock-out (KO) and wild-type (WT) mice to spinal cord contusion injury. KO and WT mice were injured with a modified New York University impactor. Weights of 10 or 5.6 g were dropped 6.25 mm onto the T13 spinal cord under isoflurane anesthesia. At 24 h, homogenized spinal cords were analyzed for total potassium concentration to estimate lesion volumes. Expression of apoptotic genes, proinflammatory cytokines, and nerve growth factors was measured by reverse transcription (RT)-PCR and Western blot. In a series of animals, locomotor recovery was assessed with the Basso mouse scale (BMS) for 6 weeks, and histological analyses was performed to determine tissue preservation. Lesion volume showed no significant differences between KO and WT mice at 24 h. RT-PCR indicated that KO mice had significantly less Bcl-2, tumor necrosis factor-␣, interleukin-1␤, and interleukin-6 mRNA compared with WT controls. Western blot also showed that KO had significantly less Bcl-2 7 d after spinal cord injury. KO mice had significantly worse BMS locomotor scores than WT at 6 weeks. KO mice also had a significantly reduced area of spared white matter and fewer neuronal-specific nuclear protein-positive neurons in the spinal cord surrounding the impact site. This result supports a potential neuroprotective role for OPN in the inflammatory response to spinal cord injury.

Diffusion Tensor Imaging at 3 Hours after Traumatic Spinal Cord Injury Predicts Long-Term Locomotor Recovery

“…Further investigations reported that spared white matter volume is the parameter correlating with functional outcome the most (McEwen and Springer, 2006;Schucht et al, 2002;You et al, 2003). This also holds true for mice of different genetic backgrounds (Hashimoto et al, 2007). The normal hindlimb motor function in both rats (Basso et al, 1996) and mice (Nishi et al, 2007) have been reported, with greater than 50-60% of spared white matter measured using post-mortem histology.…”

Glucocorticoid Protection of Oligodendrocytes against Excitotoxin Involving Hypoxia-Inducible Factor-1 in a Cell-Type-Specific Manner

“…SCI was conducted using a New York University Impactor (Hashimoto et al, 2007) to injure rat spinal cord at T9 -T10 . Sprague Dawley rats (9 weeks old) were randomly divided into three groups: the sham control, SCI, and SCI with MP treatment groups.…”

Osteopontin Mediates Citrobacter rodentium-Induced Colonic Epithelial Cell Hyperplasia and Attaching-Effacing Lesions

“…This cytokine is highly expressed in chronic inflammatory and autoimmune diseases 1 and is localized in and around inflammatory cells. 2 OPN is believed to exacerbate inflammation in a variety of settings, including infectious diseases.…”

“…2 OPN is believed to exacerbate inflammation in a variety of settings, including infectious diseases. 1 It is involved in recruiting inflammatory cells to sites of injury, as indicated by a decrease in macrophage infiltration in ischemic kidneys in OPN-deficient (OPN Ϫ/Ϫ ) mice. 1 OPN is also involved in controlling expression of inflammatory mediators, such as downregulation of the anti-inflammatory cytokine interleukin (IL)-10 and an increase in levels of the T H 1 cytokine interferon (IFN)␥.…”

“…1 It is involved in recruiting inflammatory cells to sites of injury, as indicated by a decrease in macrophage infiltration in ischemic kidneys in OPN-deficient (OPN Ϫ/Ϫ ) mice. 1 OPN is also involved in controlling expression of inflammatory mediators, such as downregulation of the anti-inflammatory cytokine interleukin (IL)-10 and an increase in levels of the T H 1 cytokine interferon (IFN)␥. 3 Accumulating evidence indicates that defects in the dynamic balance between organisms in the commensal intestinal microbiota and host innate defensive responses at the intestinal mucosal surface results in the induction of inflammatory bowel diseases (IBD).…”