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Bone & Joint Research
Vol. 13, Issue 2 | Pages 66 - 82
5 Feb 2024
Zhao D Zeng L Liang G Luo M Pan J Dou Y Lin F Huang H Yang W Liu J

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Methods

Six sets of gene expression profiles were obtained from the Gene Expression Omnibus database. Differential expression analysis, weighted gene coexpression network analysis (WGCNA), and multiple machine-learning algorithms were used to screen crucial genes in osteoarthritic cartilage, and genome enrichment and functional annotation analyses were used to decipher the related categories of gene function. Single-sample gene set enrichment analysis was performed to analyze immune cell infiltration. Correlation analysis was used to explore the relationship among the hub genes and immune cells, as well as markers related to articular cartilage degradation and bone mineralization.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 149 - 156
4 Apr 2024
Rajamäki A Lehtovirta L Niemeläinen M Reito A Parkkinen J Peräniemi S Vepsäläinen J Eskelinen A

Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Methods

Periprosthetic metal concentrations in the synovia and histopathological samples were analyzed from 230 patients from our institution from October 2016 to December 2019. An ordinal regression model was calculated to investigate the effect of the accumulated metals on the histopathological reaction of the synovia.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 279 - 293
7 Jun 2024
Morris JL Letson HL McEwen PC Dobson GP

Aims

Adenosine, lidocaine, and Mg2+ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Methods

Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed.


Bone & Joint Research
Vol. 10, Issue 4 | Pages 269 - 276
1 Apr 2021
Matsubara N Nakasa T Ishikawa M Tamura T Adachi N

Aims

Meniscal injuries are common and often induce knee pain requiring surgical intervention. To develop effective strategies for meniscus regeneration, we hypothesized that a minced meniscus embedded in an atelocollagen gel, a firm gel-like material, may enhance meniscus regeneration through cell migration and proliferation in the gel. Hence, the objective of this study was to investigate cell migration and proliferation in atelocollagen gels seeded with autologous meniscus fragments in vitro and examine the therapeutic potential of this combination in an in vivo rabbit model of massive meniscus defect.

Methods

A total of 34 Japanese white rabbits (divided into defect and atelocollagen groups) were used to produce the massive meniscus defect model through a medial patellar approach. Cell migration and proliferation were evaluated using immunohistochemistry. Furthermore, histological evaluation of the sections was performed, and a modified Pauli’s scoring system was used for the quantitative evaluation of the regenerated meniscus.


The Bone & Joint Journal
Vol. 102-B, Issue 10 | Pages 1331 - 1340
3 Oct 2020
Attard V Li CY Self A Mann DA Borthwick LA O’Connor P Deehan DJ Kalson NS

Aims

Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties.

Methods

Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosis1 (n = 8) underwent an MRI scan with advanced metal suppression (Slice Encoding for Metal Artefact Correction, SEMAC) with gadolinium contrast. Fibrotic tissue (low intensity on T1 and T2, low-moderate post-contrast enhancement) was quantified (presence and tissue thickness) in six compartments: supra/infrapatella, medial/lateral gutters, and posterior medial/lateral.


The Bone & Joint Journal
Vol. 101-B, Issue 7 | Pages 824 - 831
1 Jul 2019
Mahmoud EE Adachi N Mawas AS Deie M Ochi M

Aim

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

Materials and Methods

Two months after bilateral section of the ACL of Japanese white rabbits aged nine months or more, either phosphate buffered saline (PBS) or 1 x 106 MSCs were injected into the knee joint in single or three consecutive doses. After two months, the articular cartilage and meniscus were assessed macroscopically, histologically, and immunohistochemically using collagen I and II.


The Bone & Joint Journal
Vol. 102-B, Issue 1 | Pages 132 - 136
1 Jan 2020
Hommel H Becker R Fennema P Kopf S

Aims

We report the natural course of Baker’s cysts following total knee arthroplasty (TKA) at short- and mid-term follow-up.

Methods

In this prospective case series, 105 TKA patients were included. All patients who received surgery had a diagnosis of primary osteoarthritis and had preoperatively presented with a Baker’s cyst. Sonography and MRI were performed to evaluate the existence and the gross size of the cyst before TKA, and sonography was repeated at a mean follow-up time of 1.0 years (0.8 to 1.3; short-term) and 4.9 years (4.0 to 5.6; mid-term) after TKA. Symptoms potentially attributable to the Baker’s cyst were recorded at each assessment.


The Bone & Joint Journal
Vol. 96-B, Issue 10 | Pages 1319 - 1324
1 Oct 2014
Oh JS Youm YS Cho SD Choi SW Cho YJ

Previous studies support the important role of vascular endothelial growth factor (VEGF) and syndecan-4 in the pathogenesis of osteoarthritis (OA). Both VEGF and syndecan-4 are expressed by chondrocytes and both are involved in the regulation of matrix metalloproteinase-3, resulting in the activation of aggrecanase II (ADAMTS-5), which is essential in the pathogenesis of OA. However, the relationship between VEGF and syndecan-4 has not been established. As a pilot study, we assayed the expression of VEGF and syndecan-4 in cartilage samples and cultured chondrocytes from osteoarthritic knee joints and analysed the relationship between these two factors.

Specimens were collected from 21 female patients (29 knees) who underwent total knee replacement due to severe medial OA of the knee (Kellgren–Lawrence grade 4). Articular cartilage samples, obtained from bone and cartilage excised during surgery, were analysed and used for chondrocyte culture. We found that the levels of expression of VEGF and syndecan-4 mRNA did not differ significantly between medial femoral cartilage with severe degenerative changes and lateral femoral cartilage that appeared grossly normal (p = 0.443 and 0.622, respectively). Likewise, the levels of expression of VEGF and syndecan-4 mRNA were similar in cultured chondrocytes from medial and lateral femoral cartilage. The levels of expression of VEGF and syndecan-4 mRNAs were significantly and positively correlated in cartilage explant (r = 0.601, p = 0.003) but not in cultured chondrocytes. These results suggest that there is a close relationship between VEGF and syndecan-4 in the cartilage of patients with OA. Further studies are needed to determine the exact pathway by which these two factors interact in the pathogenesis of OA.

Cite this article: Bone Joint J 2014;96-B:1319–24.


Bone & Joint Research
Vol. 3, Issue 6 | Pages 203 - 211
1 Jun 2014
Onur T Wu R Metz L Dang A

Objectives

Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model.

Methods

T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis.


The Journal of Bone & Joint Surgery British Volume
Vol. 90-B, Issue 9 | Pages 1186 - 1192
1 Sep 2008
Lyu S

The outcome of arthroscopic medial release of 255 knees in 173 patients for varying grades of osteoarthritis involving the medial compartment is reported. All operations were performed by a single surgeon between January 2001 and May 2003. The Knee Society score for pain and the patient’s subjective satisfaction were used for the outcome evaluation. Overall, satisfactory outcome was reported for 197 knees (77.3%) and the mean Knee Society score for pain improved from 17.6 (95% confidence interval, 16.7 to 18.5), pre-operatively to 39.4 (95% confidence interval, 37.9 to 41.1) (p < 0.001). There were minor manageable complications of persistent effusion in 16 knees and prolonged wound discomfort in 11. In total, 15 of the 21 knees with poor results were converted to total knee replacements and two other patients (three knees) were offered this option after a mean period of 16 months.

Based on these observations arthroscopic medial release is an effective treatment for osteoarthritis of the medial compartment of the knee joint and can be expected to reduce the pain in the majority of patients for at least four years post-operatively.


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 488 - 492
1 Apr 2012
Vijayan S Bartlett W Bentley G Carrington RWJ Skinner JA Pollock RC Alorjani M Briggs TWR

Matrix-induced autologous chondrocyte implantation (MACI) is an established technique used to treat osteochondral lesions in the knee. For larger osteochondral lesions (> 5 cm2) deeper than approximately 8 mm we have combined the use of two MACI membranes with impaction grafting of the subchondral bone. We report our results of 14 patients who underwent the ‘bilayer collagen membrane’ technique (BCMT) with a mean follow-up of 5.2 years (2 to 8). There were 12 men and two women with a mean age of 23.6 years (16 to 40). The mean size of the defect was 7.2 cm2 (5.2 to 12 cm2) and were located on the medial (ten) or lateral (four) femoral condyles. The mean modified Cincinnati knee score improved from 45.1 (22 to 70) pre-operatively to 82.8 (34 to 98) at the most recent review (p < 0.05). The visual analogue pain score improved from 7.3 (4 to 10) to 1.7 (0 to 6) (p < 0.05). Twelve patients were considered to have a good or excellent clinical outcome. One graft failed at six years.

The BCMT resulted in excellent functional results and durable repair of large and deep osteochondral lesions without a high incidence of graft-related complications.


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 9 | Pages 1165 - 1171
1 Sep 2007
Gohil S Annear PO Breidahl W

Animal studies have shown that implanted anterior cruciate ligament (ACL) grafts initially undergo a process of revascularisation prior to remodelling, ultimately increasing mechanical strength. We investigated whether minimal debridement of the intercondylar notch and the residual stump of the ruptured ACL leads to earlier revascularisation in ACL reconstruction in humans. We undertook a randomised controlled clinical trial in which 49 patients underwent ACL reconstruction using autologous four-strand hamstring tendon grafts. Randomised by the use of sealed envelopes, 25 patients had a conventional clearance of the intercondylar notch and 24 had a minimal debridement method. Three patients were excluded from the study. All patients underwent MR scanning postoperatively at 2, 6 and 12 months, together with clinical assessment using a KT-1000 arthrometer and International Knee Documentation Committee (IKDC) evaluation. All observations were made by investigators blinded to the surgical technique. Signal intensity was measured in 4 mm diameter regions of interest along the ACL graft and the mid-substance of the posterior cruciate ligament.

Our results indicate that minimal debridement leads to earlier revascularisation within the mid-substance of the ACL graft at two months (paired t-test, p = 0.002). There was a significant reduction of mid-substance signal six months after the minimal debridement technique (paired t-test, p = 0.00007). No statistically significant differences were found in tunnel placement, incidence of Cyclops lesions, blood loss, IKDC scores, range of movement or Lachman test between the two groups.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1065 - 1070
1 Aug 2011
Tanavalee A Honsawek S Rojpornpradit T Sakdinakiattikoon M Ngarmukos S

We compared inflammation in the knee after total knee replacement (TKR) for primary osteoarthritis between two groups of patients undergoing joint replacement with and without synovectomy. A total of 67 patients who underwent unilateral TKR were randomly divided into group I, TKR without synovectomy, and group II, TKR with synovectomy. Clinical outcomes, serial serum inflammatory markers (including interleukin-6 (IL-6), CRP and ESR) and the difference in temperature of the skin of the knee, compared with the contralateral side, were sequentially evaluated until 26 weeks after surgery.

Pre-operatively, there were no statistically different clinical parameters between groups I and II. At the 26-week follow-up, both groups had a similarly significantly improved American Knee Society clinical score (p < 0.001) and functional score (p < 0.001) with no differences between the groups. Similar changes in serial inflammatory markers were found in both groups, including mean peak levels of IL-6 (189 pg/ml (sd 53.4) versus 201 pg/ml (sd 49.4) for groups I and II, respectively) and CRP (91 mg/L (sd 24.1) versus 88 mg/L (sd 23.4), respectively) on the first post-operative day, returning to pre-operative values at two and six weeks, respectively. The mean peak level of ESR for the respective two groups was 46 mm/hr versus 48 mm/hr at two weeks, which had still not returned to its pre-operative mean value at 26 weeks. The elevation in the skin temperature appeared to mirror the peak elevation of the ESR, with a range of 2.5° C to 4.5° C with some reduction at 26 weeks but still exceeding the pre-operative value.

We concluded that synovectomy at the time of TKR does not provide any benefit to the clinical outcome or shorten the duration of the inflammatory response after surgery.


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 8 | Pages 1054 - 1059
1 Aug 2011
van Jonbergen HPW Scholtes VAB van Kampen A Poolman RW

The efficacy of circumpatellar electrocautery in reducing the incidence of post-operative anterior knee pain is unknown. We conducted a single-centre, outcome-assessor and patient-blinded, parallel-group, randomised, controlled trial to compare circumpatellar electrocautery with no electrocautery in total knee replacement in the absence of patellar resurfacing. Patients requiring knee replacement for primary osteoarthritis were randomly assigned circumpatellar electrocautery (intervention group) or no electrocautery (control group). The primary outcome measure was the incidence of anterior knee pain. A secondary measure was the standardised clinical and patient-reported outcomes determined by the American Knee Society scores and the Western Ontario and McMaster Universities (WOMAC) osteoarthritis index. A total of 131 knees received circumpatellar electrocautery and 131 had no electrocautery.

The overall incidence of anterior knee pain at follow-up at one year was 26% (20% to 31%), with 19% (12% to 26%) in the intervention group and 32% (24% to 40%) in the control group (p = 0.02). The relative risk reduction from electrocautery was 40% (9% to 61%) and the number needed to treat was 7.7 (4.3 to 41.4). The intervention group had a better mean total WOMAC score at follow-up at one year compared with the control group (16.3 (0 to 77.7) versus 21.6 (0 to 76.7), p = 0.04). The mean post-operative American Knee Society knee scores and function scores were similar in the intervention and control groups (knee score: 92.4 (55 to 100) versus 90.4 (51 to 100), respectively (p = 0.14); function score: 86.5 (15 to 100) versus 84.5 (30 to 100), respectively (p = 0.49)).

Our study suggests that in the absence of patellar resurfacing electrocautery around the margin of the patella improves the outcome of total knee replacement.


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 5 | Pages 634 - 638
1 May 2010
Savarino L Tigani D Greco M Baldini N Giunti A

We investigated the role of ion release in the assessment of fixation of the implant after total knee replacement and hypothesised that ion monitoring could be a useful parameter in the diagnosis of prosthetic loosening. We enrolled 59 patients with unilateral procedures and measured their serum aluminium, titanium, chromium and cobalt ion levels, blinded to the clinical and radiological outcome which was considered to be the reference standard. The cut-off levels for detection of the ions were obtained by measuring the levels in 41 healthy blood donors who had no implants. Based on the clinical and radiological evaluation the patients were divided into two groups with either stable (n = 24) or loosened (n = 35) implants.

A significant increase in the mean level of Cr ions was seen in the group with failed implants (p = 0.001). The diagnostic accuracy was 71% providing strong evidence of failure when the level of Cr ions exceeded the cut-off value. The possibility of distinguishing loosening from other causes of failure was demonstrated by the higher diagnostic accuracy of 83%, when considering only patients with failure attributable to loosening.

Measurement of the serum level of Cr ions may be of value for detecting failure due to loosening when the diagnosis is in doubt. The other metal ions studies did not have any diagnostic value.