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1.  Toll-like receptors in human chondrocytes and osteoarthritic cartilage 
Acta Orthopaedica  2013;84(6):585-592.
Background and purpose
Degenerating 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.
We 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.
In 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).
Mature 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.
PMCID: PMC3851674  PMID: 24237425
2.  Prevention of deep infection in joint replacement surgery 
Acta Orthopaedica  2010;81(6):660-666.
PMCID: PMC3216074  PMID: 21110700
3.  Younger age increases the risk of early prosthesis failure following primary total knee replacement for osteoarthritis 
Acta Orthopaedica  2010;81(4):413-419.
Background and purpose
Total knee replacements (TKRs) are being increasingly performed in patients aged ≤ 65 years who often have high physical demands. We investigated the relation between age of the patient and prosthesis survival following primary TKR using nationwide data collected from the Finnish Arthroplasty Register.
From Jan 1, 1997 through Dec 31, 2003, 32,019 TKRs for primary or secondary osteoarthritis were reported to the Finnish Arthroplasty Register. The TKRs were followed until the end of 2004. During the follow-up, 909 TKRs were revised, 205 (23%) due to infection and 704 for other reasons.
Crude overall implant survival improved with increasing age between the ages of 40 and 80. The 5-year survival rates were 92% and 95% in patients aged ≤ 55 and 56–65 years, respectively, compared to 97% in patients who were > 65 years of age (p < 0.001). The difference was mainly attributable to reasons other than infections. Sex, diagnosis, type of TKR (condylar, constrained, or hinge), use of patellar component, and fixation method were also associated with higher revision rates. However, the differences in prosthesis survival between the age groups ≤ 55, 56–65, and > 65 years remained after adjustment for these factors (p < 0.001).
Young age impairs the prognosis of TKR and is associated with increased revision rates for non-infectious reasons. Diagnosis, sex, type of TKR, use of patellar component, and fixation method partly explain the differences, but the effects of physical activity, patient demands, and obesity on implant survival in younger patients warrant further research.
PMCID: PMC2917562  PMID: 20809740
4.  BMPs in periprosthetic tissues around aseptically loosened total hip implants 
Acta Orthopaedica  2010;81(4):420-426.
Background and purpose
Primary and dynamically maintained periprosthetic bone formation is essential for osseointegration of hip implants to host bone. Bone morphogenetic proteins (BMPs) play a role in osteoinductive bone formation. We hypothesized that there is an increased local synthesis of BMPs in the synovial membrane-like interface around aseptically loosened total hip replacement (THR) implants, as body attempts to generate or maintain implant fixation.
Patients and methods
We compared synovial membrane-like interface tissue from revised total hip replacements (rTHR, n = 9) to osteoarthritic control synovial membrane samples (OA, n = 11. Avidin-biotin-peroxidase complex staining and grading of BMP-2, BMP-4, BMP-6, and BMP-7 was done. Immunofluorescence staining was used to study BMP proteins produced by mesenchymal stromal/stem cells (MSCs) and osteoblasts.
Results and interpretation
All BMPs studied were present in the synovial lining or lining-like layer, fibroblast-like stromal cells, interstitial macrophage-like cells, and endothelial cells. In OA and rTHR samples, BMP-6 positivity in cells, inducible by the proinflammatory cytokines tumor necrosis factor−α and interleukin-1β, predominated over expression of other BMPs. Macrophage-like cells positive for BMP-4, inducible in macrophages by stimulation with particles, were more frequent around loosened implants than in control OA samples, but apparently not enough to prevent loosening. MSCs contained BMP-2, BMP-4, BMP-6, and BMP-7, but this staining diminished during osteogenesis, suggesting that BMPs are produced by progenitor cells in particular, probably for storage in the bone matrix.
PMCID: PMC2917563  PMID: 20515435
5.  Whole-mount specimens in the analysis of en bloc samples obtained from revisions of resurfacing hip implants 
Acta Orthopaedica  2010;81(3):324-330.
Modern metal-on-metal hip resurfacing implants are being increasingly used for young and active patients, although the long-term outcome and failure mechanisms of these implants are still unknown. In this consecutive revision case series, early failures of femoral implants (at < 4 years) were studied.
3 revisions were done due to a fracture of the femoral neck and 1 due to loosening and varus position of the femoral component. Femoral heads were removed en bloc 2–46 months after the primary operation, embedded in methylmethacrylate, sectioned, stained, and analyzed as whole-mount specimens in 4 55–62-year-old patients with osteoarthritis.
Histopathology was characterized by new but also partly healed trabecular microfractures, bone demineralization, cysts, metallosis, and abnormal formation of new woven bone. All samples displayed signs of notching, osteoporosis, and aseptic necrosis, which seemed to have been the main reason for the subsequent development and symptoms of the patients and revision operations of the hips.
Based on these early revision cases, it appears that aseptic necrosis is a common cause of early loosening of resurfacing hip implants.
PMCID: PMC2876834  PMID: 20367416
6.  Low rate of infected knee replacements in a nationwide series—is it an underestimate? 
Acta Orthopaedica  2009;80(2):205-212.
Background and purpose Specialist hospitals have reported an incidence of early deep infections of < 1% following primary knee replacement. The purpose of this study was to estimate the infection rate in a nationwide series using register-based data.
Methods The Finnish Arthroplasty Register (FAR) was searched for primary unicompartmental, total, and revision knee arthroplasties performed in 1997 through 2003 and eventual revision arthroplasties. The FAR data on revision arthroplasties was supplemented by a search of the national Hospital Discharge Register (HDR) for debridements, partial and total revision knee replacements, resection arthroplasties, arthrodeses, and amputations.
Results During the first postoperative year, 0.33% (95% CI: 0.13–0.84), 0.52% (0.45–0.60) and 1.91% (1.40–2.61) of the primary UKAs, primary TKAs, and revision TKAs, respectively, were reoperated due to infection. The 1-year rate of reoperations due to infection remained constant in all arthroplasty groups over the observation period.
The overall infection rate calculated using FAR data only was 0.77% (95% CI: 0.69–0.86), which was lower, but was not, however, statistically significantly different from the overall infection rate calculated using endpoint data combined from FAR and HDR records (0.89%; 95% CI: 0.80–0.99). FAR registered revision arthroplasties and patellar resurfacing arthroplasties reliably but missed a considerable proportion of other reoperations.
Interpretation More reoperations performed due to infection can be expected as the numbers of knee arthroplasties increase, since there has been no improvement in the early infection rate. Finnish Arthroplasty Register data appear to underestimate the incidence of reoperations performed due to infection.
PMCID: PMC2823163  PMID: 19404805
7.  Outcome of prosthesis exchange for infected knee arthroplasty: the effect of treatment approach 
Acta Orthopaedica  2009;80(1):67-77.
Background and purpose Two-stage revision remains the gold standard in the treatment of infected knee arthroplasty. Lately, good long-term results of direct exchange arthroplasty have been reported. The purpose of this literature review is to compare the clinical outcome achieved with one-stage revision and two-stage revision with different types of spacers.
Methods A thorough systematic review of literature was undertaken to idenepsy reports on the treatment alternatives. Papers written in English or including an English abstract, published from 1980 through 2005, and reporting either the success rate in eradication of infection or the clinical status achieved were reviewed. 31 original articles describing the results of 154 one-stage exchange arthoplasties and of 926 two-stage exchange arthoplasties were included. The depth of detail in the description of materials and methods varied markedly, making it impossible to perform a meta-analysis. Instead, a descriptive review of the results is presented.
Results With a follow-up of 12–122 months, the overall success rate in eradication of infection was 73–100% after one-stage revisions and 82–100% after two-stage revisions. Reinfection rates were the lowest in series where articulating cement spacers were used, though the follow-up was relatively short. Studies using articulating spacers reported the highest average postoperative ranges of motion. Otherwise, no correlations were observed between the clinical outcome and the length of follow-up, the type of revision, or the type of spacer. The clinical outcome (knee scores and range of motion) of the one-stage revisions was no different from that of the two-stage revisions.
Interpretation Two-stage exchange is an effective treatment. Mobile spacers may further improve the range of motion. More experience in one-stage revision is required in order to define its role in the management of infected knee arthroplasties.
PMCID: PMC2823239  PMID: 19234888

Results 1-7 (7)