We surgically treated 16 patients with Bertolotti's syndrome (chronic, persistent low back pain and radiographically diagnosed transitional lumbar vertebra). Eight had posterolateral fusion and another eight resection of the transitional articulation. Thirteen patients had in addition to the chronic low back pain, suffered from repeated episodes or chronic sciatica. In six cases with resection treatment, local injections were administered at the transitional articulation before deciding for resection of the transitional joint; each patient reported transient relief of pain, while this preoperative test did not correlate with successful outcome of treatment. Six patients had to be treated with second operations. Ten of the 16 operatively treated patients showed improvement of the low back pain, and this result was similar in the group treated with fusion and in that treated with resection. Seven had no low back pain at follow-up, and the improvement according to the Oswestry pain scale was similar in the two groups, and statistically significant. Eleven patients still had persisting episodes of sciatica (versus 13 preoperatively). The average disability according to the Oswestry total disability scale was 30%, corresponding with moderate outcome, and both operatively treated groups did equally well. At follow-up the first disc above the fused segments was found to be degenerated in seven out of eight cases, and in the group treated with resection the first disc above the transitional vertebra was degenerated in five cases.(ABSTRACT TRUNCATED AT 250 WORDS)
Background and purposeDegenerating cartilage releases potential danger signals that react with Toll-like receptor (TLR) type danger receptors. We investigated the presence and regulation of TLR1, TLR2, and TLR9 in human chondrocytes.MethodsWe studied TLR1, TLR2, TLR4, and TLR9 mRNA (qRT-PCR) and receptor proteins (by immunostaining) in primary mature healthy chondrocytes, developing chondrocytes, and degenerated chondrocytes in osteoarthritis (OA) tissue sections of different OARSI grades. Effects of a danger signal and of a pro-inflammatory cytokine on TLRs were also studied.ResultsIn primary 2D-chondrocytes, TLR1 and TLR2 were strongly expressed. Stimulation of 2D and 3D chondrocytes with a TLR1/2-specific danger signal increased expression of TLR1 mRNA 1.3- to 1.8-fold, TLR2 mRNA 2.6- to 2.8-fold, and TNF-α mRNA 4.5- to 9-fold. On the other hand, TNF-α increased TLR1 mRNA] expression 16-fold, TLR2 mRNA expression 143- to 201-fold, and TNF-α mRNA expression 131- to 265-fold. TLR4 and TLR9 mRNA expression was not upregulated. There was a correlation between worsening of OA and increased TLR immunostaining in the superficial and middle cartilage zones, while chondrocytes assumed a CD166× progenitor phenotype. Correspondingly, TLR expression was high soon after differentiation of mesenchymal stem cells to chondrocytes. With maturation, it declined (TLR2, TLR9).InterpretationMature chondrocytes express TLR1 and TLR2 and may react to cartilage matrix/chondrocyte-derived danger signals or degradation products. This leads to synthesis of pro-inflammatory cytokines, which stimulate further TLR and cytokine expression, establishing a vicious circle. This suggests that OA can act as an autoinflammatory disease and links the old mechanical wear-and-tear concept with modern biochemical views of OA. These findings suggest that the chondrocyte itself is the earliest and most important inflammatory cell in OA.
BackgroundSoluble biglycan (sBGN) and soluble decorin (sDCN), are two closely related essential components of extracellular matrix which both have been shown to possess proinflammatory properties. We studied whether sBGN or sDCN were present in synovial fluid (SF) of osteoarthritis (OA) or rheumatoid arthritis (RA) patients and studied sBGN or sDCN potential role in the degradation of OA cartilage.MethodsSF obtained from meniscus tear, OA, and RA patients were analysed for sBGN and sDCN using enzyme-linked immunosorbent assays. OA chondrocytes and cartilage explants were stimulated for 48 h with 5 μg/ml sBGN or 1 μg/ml lipopolysaccharide. Messenger RNA (mRNA) levels of Toll-like receptors (TLRs), proteinases and cartilage matrix molecules were determined using quantitative real-time polymerase chain reaction. Protein levels of matrix metalloproteinases (MMPs) and cytokines were measured using Luminex xMap technology. Production of nitric oxide (NO), release of proteoglycans and soluble collagen were measured from conditioned culture media using biochemical assays. OA cartilage explant proteoglycans were stained for Safranin O and quantified using image analysis. TLR4 activation by sBGN and sDCN was studied in engineered HEK-293 cells with TLR4 signalling genes inserted together with a reporter gene.ResultssBGN was found in meniscus tear SF (14 ± 2 ng/ml), OA SF (582 ± 307 ng/ml) and RA SF (1191 ± 482 ng/ml). Low levels of sDCN could also be detected in SF of meniscus tear (51 ± 4) ng/ml, OA (52 ± 3 ng/ml), and RA (49 ± 4 ng/ml). Stimulation of chondrocytes with sBGN increased significantly the mRNA and protein expression of catabolic MMPs, including MMP1, MMP9 and MMP13, and of inflammatory cytokines interleukin (IL)-6 and IL-8, whereas the expression of anabolic markers aggrecan and collagen type II was decreased. sBGN induced release of proteoglycans, collagen and NO from chondrocytes and cartilage explants. The catabolic response in explants was dependent of OA cartilage degradation stage. The mechanism of action of sBGN was mainly mediated through the TLR4-nuclear factor-κB pathway.ConclusionsHigh levels of sBGN was found in advanced OA and RA SF. sBGN activates chondrocytes mainly via TLR4, which results in net loss of cartilage. Thus, sBGN can be a mediator of OA cartilage degradation and also a potential biomarker for arthritis.
We have reviewed retrospectively 68 revisions of the femoral component in arthroplasties of the hip in 65 patients, using impaction bone grafting, at a median of three years (1 month to 6 years). We employed the cemented Exeter X-Change technique in 36 patients and the uncemented Bi-Metric allografting method in 32. The 37 bone defects were grade 3 or grade 4 on the Endo-Klinik classification. The Mayo hip score improved from a mean of 32 (SD +/- 18) to 62 (SD +/- 15). Most (25) of the 34 complications occurred in grade-3 and grade-4 defects; nine were intraoperative diaphyseal fractures and eight fractures of the greater trochanter. All the fractures united. The risk of intraoperative fracture was prevented by supporting the bone with wires in 16 hips, with reinforcement mesh in 18 and by a plate in six. Early migration of the stem of more than 10 mm during the first year indicated rotational instability; it occurred in three cases. In difficult revision cases with large defects of the femoral bone, bone-impaction techniques carry a high risk of complications.
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