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Background: The aim of this study was to understand how facet joint orientation (FJO) and facet joint tropism (FJT) affected severe intervertebral disc degeneration (IVDD) process at lower lumbar l...

Schmorl's nodes (SNs) have increasingly been recognized on vertebral end-plates using advanced imaging techniques. Even though vertebral end-plates are the closest structures to discs, their pathologies are underestimated in the etiology of low back pain (LBP). We aimed to detect the prevalence of SNs and other end-plate defects in subjects with/without LBP and to understand whether SNs were associated with LBP and spinal degeneration. Subjects were evaluated in terms of end-plate defects, intervertebral disc degeneration (IVDD), and vertebral end-plate changes (Modic changes) at all lumbar levels on lumbar spine magnetic resonance imagings (MRI). Control subjects were compared to patients with LBP. Higher Pfirrmann scores (OR: 2.696) and higher SN scores (OR: 8.076) were significantly associated with Modic changes at L4-L5 disc level. Patients with higher SN scores at L1-L2 or L2-L3 levels had approximately 7-fold increased risk of severe IVDD at the corresponding levels. The most significant factor associated with presence of SNs was body weight of the patients (OR: 1.417). The most significant factor associated with intensity of LBP was severe IVDD at L5-S1 level (OR: 3.670). Having higher total SN score had an OR of 1.230 (95% CI: 1.003-1.509; p = 0.047) for predicting LBP. Schmorl's nodes were seen in 33.1% of patients and 11.5% of asymptomatic subjects. Body weight was the most significant factor associated with SNs. The most significant factor associated with LBP was severe IVDD at L5-S1 level.

Objectives The prevalence of low-back pain (LBP) in adolescents ranges from 7 to 72%. We aimed to define the radiologic characteristics of the lumbar spine in children and adolescents with LBP with/without leg pain. Methods Two hundred and fourteen children and adolescents, who were born between 2001 and 2009 and had lumbar spine MRI for LBP with/without leg pain, were evaluated in terms of intervertebral disc degeneration (IVDD), end-plates and paraspinal muscle changes on lumbar spine MRIs. Results Severe IVDD was detected at all lumbar levels except for L2-L3. Modic changes were present in 4.2% of the patients. Modic changes were more common in patients with severe IVDD than in those with mild-to-moderate IVDD. Severe IVDD was significantly associated with Modic changes at the corresponding L1-L2 and L3-L4 disc levels. Girls had significantly more fatty infiltration in the paraspinal muscles when compared to boys. The risk of having severe IVDD concomitant with Modic changes was high [odds ratio (OR), 8.6]. The OR was 20.7 for predicting the presence of severe IVDD at any level if Modic changes presented particularly at the L3-L4 level. The ORs of Modic changes presented at any lumbar level at the background of fat-infiltrated multifidus at L3-L4 and L4-L5 levels were 8.3 and 9.1, respectively. Conclusions Fatty infiltration in the paraspinal muscles and IVDD were closely associated with Modic changes in children and adolescents with LBP. Lumbar IVDD in children and adolescents could be the result of a mechanical pathology.

Background School scoliosis screening programs (SSSPs) are widely used for reporting the prevalence and improving the awareness of scoliosis. Thus, scoliosis could be prevented and/or treated in a timely manner. However, mild scoliosis (10°–20°) could be missed in SSSPs. Previously obtained plain chest radiographs could be used as an adjunct to SSSPs to detect the exact prevalence of scoliosis. In this study, we aimed to detect the prevalence of thoracic scoliosis in adolescents in Turkey using posteroanterior chest radiographs. Methods We conducted a cross-sectional radiologic study evaluating plain chest radiographs in adolescents who visited the emergency department or outpatient clinics at a community-based hospital. We also reviewed the literature regarding scoliosis screening in adolescents using the PubMed/MEDLINE search engine. Results We included 1065 adolescents. Thoracic scoliosis was detected on plain posteroanterior chest radiographs in 10.4% of the adolescents. The prevalence of thoracic scoliosis was significantly larger in females compared with males (12.3% vs. 8.6%; P = 0.047). We retrieved 140 articles regarding scoliosis screening in adolescents from the literature. Each continent had different scoliosis prevalence (according to Cobb angle ≥10° verified on a radiograph). Conclusions SSSPs help detection of the prevalence of scoliosis and the factors associated with scoliosis in adolescents. However, patients with small-angle curves could be missed in SSSPs. Our results showed that plain posteroanterior chest radiographs could be used as an adjunct to SSSPs to accurately detect prevalence of scoliosis in adolescents.

National audience; Most G-protein-coupled receptors (GPCRs) form di(oligo)-meric structures that constitute signaling and trafficking units and might be essential for receptor functions. Cell responses to complement C5a receptor (C5aR) are tightly controlled by receptor desensitization and internalization. To examine the implication of dimerization in C5aR regulation, we generated an NH(2)-terminally modified C5aR mutant, unable to bind C5a, and a phosphorylation-deficient mutant. Neither an intact NH(2) terminus nor the presence of COOH-terminal phosphorylation sites appeared to be required for the formation of C5aR dimers. Upon C5a stimulation, mutant receptors did not internalize when individually expressed. C5a stimulation of cells that co-expressed wild type C5aR together with either unliganded or phosphorylation-deficient mutant resulted in co-internalization of mutant receptors with C5aR. Unliganded GPCRs can be cross-phosphorylated within a heterologous receptor dimer or by second messenger-activated kinases. C5a stimulation of (32)P-labeled cells that co-expressed the unliganded mutant with either C5aR or the phosphorylation-deficient mutant did not induce phosphorylation of the unliganded mutant. We can thus postulate that, in the case of C5aR, the stimulation and phosphorylation of one monomer is enough to lead to dimer internalization. The existence and functional implication of di(oligo)mer formation may be important for an accurate C5aR down-regulation in pathological conditions.

The N-formyl peptide receptor-like 1 (FPRL1) is a G protein-coupled receptor (GPCR) that transmits intracellular signals in response to a variety of agonists, many of them being clearly implicated in human pathology. beta-arrestins are adaptor proteins that uncouple GPCRs from G protein and regulate receptor internalization. They can also function as signal transducers through the scaffolding of signaling molecules, such as components of the extracellular signal-regulated kinase (ERK) cascade. We investigated the role of beta-arrestins in ligand-induced FPRL1 internalization and signaling. In HEK293 cells expressing FPRL1, fluorescence microscopy revealed that agonist-stimulated FPRL1 remained co-localized with beta-arrestins during endocytosis. Internalization of FPRL1, expressed in a mouse embryonic fibroblast (MEF) cell line lacking endogenous beta-arrestins, was highly compromised. This distinguishes FPRL1 from the prototypical formyl peptide receptor FPR that is efficiently internalized in the absence of beta-arrestins. In both HEK293 and MEF cells, FPRL1-mediated ERK1/2 activation was a rapid and transient event. The kinetics and extent of ERK1/2 activation were not significantly modified by beta-arrestin overexpression. The pattern of FPRL1-mediated ERK1/2 activation was similar whether cells express or not beta-arrestins. Furthermore, treatment of the FPRL1 expressing cells with pertussis toxin inhibited ERK1/2 activation in MEF and in HEK293 cells. These results led us to conclude that activation of ERK1/2 mediated by FPRL1 occurs primarily through G protein signaling. Since beta-arrestin-mediated signaling has been observed essentially for receptors coupled to G proteins other than G(i), this may be a characteristic of G(i) protein-coupled chemoattractant receptors.

Leukocyte recruitment to sites of inflammation and infection is dependent on the presence of a gradient of locally produced chemotactic factors. This review is focused on current knowledge about the activation and regulation of chemoattractant receptors. Emphasis is placed on the members of the N-formyl peptide receptor family, namely FPR (N-formyl peptide receptor), FPRL1 (FPR like-1) and FPRL2 (FPR like-2), and the complement fragment C5a receptors (C5aR and C5L2). Upon chemoattractant binding, the receptors transduce an activation signal through a G protein-dependent pathway, leading to biochemical responses that contribute to physiological defense against bacterial infection and tissue damage. C5aR, and the members of the FPR family that were previously thought to be restricted to phagocytes proved to have a much broader spectrum of cell expression. In addition to N-formylated peptides, numerous unrelated ligands were recently found to interact with FPR and FPRL1. Novel agonists include both pathogen- and host-derived components, and synthetic peptides. Antagonistic molecules have been identified that exhibit limited receptor specificity. How distinct ligands can both induce different biological responses and produce different modes of receptor activation and unique sets of cellular responses are discussed. Cell responses to chemoattractants are tightly regulated at the level of the receptors. This review describes in detail the regulation of receptor signalling and the multi-step process of receptor inactivation. New concepts, such as receptor oligomerization and receptor clustering, are considered. Although FPR, FPRL1 and C5aR trigger similar biological functions and undergo a rapid chemoattractant-mediated phosphorylation, they appear to be differentially regulated and experience different intracellular fates.