Abstract. Objectives. A promising therapy for early osteoarthritis (OA) is the transplantation of human umbilical cord-derived mesenchymal stromal cells (hUC-MSCs). The synovial fluid (SF) from a pre-clinical ovine model treated with hUC-MSCs has been profiled using proteomics and bioinformatics to elucidate potential mechanisms of therapeutic effect. Methods. Four weeks after a medial meniscus transection surgery, sheep were injected with 10. 7. hUC-MSCs in Phosphate Buffered Saline (PBS) or PBS only (n=7) and sacrificed at 12 weeks. SF was normalised for protein abundance (ProteoMiner. TM. ) and analysed using label-free quantitation proteomics. Bioinformatics analyses (Ingenuity Pathway Analysis (IPA) and STRING) were used to assess differentially regulated functions from the proteomic data. Human orthologues were identified for the ovine proteins using UniProt and DAVID resources and proteins that were ≥±1.3 fold differentially abundant between treatment groups, were included in the bioinformatics analyses. Results. hUC-MSC treated animals demonstrated significantly less joint space narrowing. Nineteen SF proteins were differentially abundant in treated cf. control sheep (FC±2.0; p<0.05). Biglycan (a small leucine-rich proteoglycan of the cartilage extracellular matrix) abundance was increased by 2.1 fold in treated compared to untreated sheep (p=0.024). IPA indicated that lipid synthesis (z-score=1.772; p=0.00267) and immune cell migration pathways (cell movement of mononuclear leukocytes: z-score=1.761; p=0.00259), amongst others, were likely to be activated in the treated sheep. Conversely, tissue damage (z-score=−2; p=0.00019), senescence (z-score=−1.981; p=0.00007) and necrosis (z-score=−1.728; p=0.00829) associated pathways as well as inflammation (z-score=−1.718; p=0.00057) and vascular permeability (z-score=−1.698; p=0.00002) were likely to be inhibited in treated cf. untreated sheep. Conclusions. hUC-MSC treatment prevented/delayed OA progression, demonstrated via a reduction in joint space narrowing. SF proteome bioinformatics revealed potential mechanisms of therapeutic action related to immunomodulation and the inhibition of multiple cell death, and tissue damage associated pathways. Further, a potential predicted upregulation in lipid synthesis in treated sheep represents a novel mechanism warranting further investigation. Additional work is required to validate these discovery phase proteomic findings in studies which specifically target and manipulate the proposed mechanisms highlighted. Declaration of Interest. (b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project

Knee joint distraction (KJD) has been associated with clinical and structural improvement and synovial fluid (SF) marker changes. However, structural changes have not yet been shown satisfactorily in regular care, since radiographic acquisition was not fully standardized. AI-based modules have shown great potential to reduce reading time, increase inter-reader agreement and therefore function as a tool for treatment outcome assessment. The objective was to analyse structural changes after KJD in patients using this AI-based measurement method, and relate these changes to clinical outcome and SF markers. 20 knee OA patients (<65 years old) were included in this study. KJD treatment was performed using an external fixation device, providing 5 mm distraction for 6 weeks. SF was aspirated before, during and immediately after treatment. Weight-bearing antero-posterior knee radiographs and WOMAC questionnaires were collected before and ~one year after treatment. Radiographs were analysed with the Knee Osteoarthritis Labelling Assistant (KOALA, IB Lab GmbH, Vienna, Austria), and 10 pre-defined biomarker levels in SF were measured by immunoassay. Radiographic one-year changes were analysed and linear regression was used to calculate associations between changes in standardized joint space width (JSW) and WOMAC, and changes in JSW and SF markers. After treatment, radiographs showed an improvement in Kellgren-Lawrence grade in 7 of 16 patients that could be evaluated; 3 showed a worsening. Joint space narrowing scores and continuous JSW measures improved especially medially. A greater improvement in JSW was significantly associated with a greater improvement in WOMAC pain (β=0.64;p=0.020). A greater increase in MCP1 (β=0.67;p=0.033) and lower increase in TGFβ1 (β=-0.787;p=0.007) were associated with JSW improvement. Despite the small number of patients, also in regular care KJD treatment shows joint repair as measured automatically on radiographs, significantly associated with certain SF marker change and even with clinical outcome

Introduction. The purpose of this study was to examine if Sugioka's transtrochanteric rotational osteotomy (TRO) of the femoral head could be a valid option in treating idiopathic osteonecrosis of the femoral head. Methods. Thirty-two TROs performed in 29 patients between 1985 and 2006 were studied. Patient age at operation ranged from 16 to 56 years (average, 36 years). Thirteen hips were in women and 19 hips in men. Height was 165 cm and weight 63 kg (Body Mass Index 23) on average. Risk factors were corticosteroid use in 18 hips and excessive alcohol consumption in 15 hips (2 of them had both backgrounds), while neither of them was found with 1 hip. Bilateral hips were affected in 19 patients and 3 of them underwent bilateral TROs sequentially. The femoral head was rotated anteriorly in 26 hips and posteriorly in 6 hips. For fixation of the osteotomy site, large femoral screws had been used till 1995 (Group 1, 9 hips), and since 1996 an AO angle plate or a compression hip screw has been used (Group 2, 13 hips). Since 2003, pre-operative planning was performed more meticulously and the distal part of the joint capsule was cut after osteotomy as described by Atsumi (Group 3, 10 hips). The average follow-up period was 6.5 years (range, 2 to 21 years). Results. The average Japanese Orthopaedic Association hip score was 55 points pre-operatively, 63 points at 1 year, and 61 points at the latest follow-up. With pain increase, re-collapse of the rotated femoral head, fracture of the proximal fragment, nonunion, trochanteric detachment, joint space narrowing, osteoarthritic changes, or infection as the endpoint, the survival rate was 58% at 1 year, 53% at 4 - 9 years. The endpoint developed in 14 hips (re-collapse of the rotated femoral head in 9, fracture of the proximal fragment in 3, joint space narrowing in 1, and infection in 1). The changes in the surgical techniques were suggested to have improved the 3-year survivorship: 25% in Group 1, 54% in Group 2, and 74% in Group 3. The 4- to 9-year survival of this procedure was 53%. The majority of the endpoints developed within the first year, which may suggest that most of them were surgery-related. Conclusion. This procedure requires precise and meticulous precautions in pre-operative planning, preservation of the posterior column vessels during surgery, capsulotomy, and after-treatment. With those precautions, this procedure could be a valid joint-reserving option in treating idiopathic osteonecrosis of the femoral head. TRO is a highly difficult procedure and should be performed only by surgeons who have full training

Summary. The dGEMRIC index correlates more strongly with the pattern of radiographic joint space narrowing in hip osteoarthritis at five year follow-up than morphological measurements of the proximal femur. It therefore offers potential to refine predictive models of hip osteoarthritis progression. Introduction. Longitudinal general population studies have shown that femoroacetabular impingement increases the risk of developing hip osteoarthritis, however, morphological parameters have a low positive predictive value. Arthroscopic debridement of impingement lesions has been proposed as a potential strategy for the prevention of osteoarthritis, however, the development of such strategies requires the identification of individuals at high risk of disease progression. We investigated whether delayed Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) predicts disease progression. This imaging modality is an indirect measure of cartilage glycosaminoglycan content. Patients and Methods. 34 asymptomatic individuals from a longitudinal cohort study (sibkids) were assessed at baseline with the collection of Patient Reported Outcome Measures (PROMs), anteroposterior and cross-table lateral radiographs, 3D morphological MRI, and dGEMRIC at 3T of their index hip. A dGEMRIC index was calculated as a ratio of the anterosuperior acetabular cartilage T1 relaxation time and the total femoral and acetabular cartilage T1 relaxation time. 29 individuals were followed up at 5 years for repeat assessment (average age 51 years and range 36 to 67). Radiological measurements were made by a single observer using in house Hipmorf software. Radiographic disease progression was assessed using minimum joint space width (JSW), lateral sourcil JSW, and medial sourcil JSW. These were measured on baseline and five year follow-up anteroposterior radiographs with an intra-observer ICC of 0.916. Alpha angle measurements were made by the same observer on radiographs and MRI radial slices with an intra-observer ICC of 0.926. Results. Mean minimum JSW for the cohort fell by 0.16mm over five years (p=0.024). Baseline dGEMRIC index did not correlate with change in minimum JSW (r=0.031 p=0.873). There was a moderate correlation between baseline dGEMRIC and the direction of JSW loss (change in JSW at the lateral sourcil minus change in JSW at the medial sourcil) (r=0.561 p=0.002). There was a weak correlation between the change in Non-Arthritic Hip Score and baseline dGEMRIC (r=0.256 P=0.180). Maximum alpha angle measured on baseline MRI radial slices did not correlate with change in minimum JSW and weakly correlated with the direction of JSW narrowing (r=0.273 p=0.160). Conclusion. A low dGEMRIC index indicates reduced glycosaminoglycan concentration in the anterosuperior acetabular cartilage compared with the total femoral and acetabular cartilage. This correlates with lateral JSW narrowing relative to medial JSW narrowing as osteoarthritis progresses. The dGEMRIC index correlates better with osteoarthritis progression than alpha angle measurements and offers the potential to refine a predictive model for osteoarthritis progression to aid patient selection for clinical trials

Introduction. Very limited treatment options are available for osteoarthritis and most of them are for symptoms of osteoarthritis not for cause. Adult mesenchymal stem cells (MSCs), which have the ability to differentiate into cells of the chondrogenic lineage, have emerged as a candidate cell type with great potential for cell-based articular cartilage repair technologies. We conducted a study to see the effect of direct injection of stem cells on artificially created osteoarthritis model in rabbits. Methods. Surgical instability was created in 20 adult white rabbits over 16 weeks old and weighing over 2 kg using a modification of the technique of Hulth et al. Only the right knees were operated (with other side serving as control). 12 weeks after surgery, X-rays were done for all 20 rabbits and confirmed for features of osteoarthritis like joint space narrowing, osteophyte formation etc. Bone marrow was aspirated and stem cells were prepared by method of Pittenger et al. Animals were divided into 2 groups of 10 each: Group I (with stem cell infusion) and Group II (control). The radiological evaluation was done at 12 week, 16 weeks, 20 weeks and histological evaluation at 16 and 20 weeks. Results. Mean radiological score in Group I at 12 week, 16 week and 20 week was 2.20±0.42, 2.8±0.42, 3.0±0.0 respectively. Mean radiological score of controls at 12 week, 16 week and 20 week was 2.40±0.51, 3.4±0.51, 3.8±0.44 respectively. On comparing mean radiological score of Group I and control at 12, 16 and 20 weeks p value comes out to be 0.481, 0.015 and 0.014 respectively, which was statically significant at 16 and 20 week. Mean histological score of Group I at 16 week and 20 week was 4.20±0.44, 5.8±0.83 respectively. Mean histological score of control at 16week and 20 week was 6.00±0.7, 9.4±0.54 respectively. On comparing mean histological score of Group I and Group II at 16 and 20 week p value comes out to be 0.009 and 0.008 respectively which was statistically significant at both 16 and 20 weeks. Conclusion. Our study using stems cell as treatment option of osteoarthritis has shown significant histopathological and radiological improvement compared to control at both follow up. Stem cells are promising source for treatment of osteoarthritis and neither stem cell culture nor scafolds are absolutely necessary for favourable outcome but larger group and longer followup are required for using stem cells as therapeutic option. Summary. Direct injection of Stem cells can reduce osteoarthritis and repair articular cartilage in Osteoarthritis

Summary. Anatomical variations in hip joint anatomy are associated with both the presence and location of tibiofemoral osteoarthritis (OA). Introduction. Variations in hip joint anatomy can alter the moment-generating capacity of the hip abductor muscles, possibly leading to changes in the magnitude and direction of ground reaction force and altered loading at the knee. Through analysis of full-limb anteroposterior radiographs, this study explored the hypothesis that knees with lateral and medial knee OA demonstrate hip geometry that differs from that of control knees without OA. Patients and Methods. This cross-sectional study is an ancillary to the Multicenter Osteoarthritis Study (MOST), an observational cohort study of incident and progressive knee OA in community-dwelling men and women, ages 50–79 years. We report on 160 knees with lateral OA (LOA), 168 knees with medial OA (MOA), and 336 controls. All participants with LOA at the baseline MOST visit were included. An equal number of knees with MOA, and twice the number of control knees were then randomly selected. In participants with bilateral eligibility, a single knee was randomly selected so that all participants contributed only one case or one control knee to the analysis. Case knees were identified as having Kellgren/Lawrence (K/L) ≥ 2 with joint space narrowing (JSN) ≥ 1 in the specified compartment with no JSN in the adjoining compartment. Controls had no radiographic OA (K/L=0 or 1 and JSN=0) in either compartment. Hip joint anatomy parameters were assessed from full-limb standing radiographs using custom OsiriX software by an author (AB) blinded to knee OA status, and unreadable radiographs (N = 8) were discarded prior to unblinding. We measured parameters that influence the abductor moment arm of the hip, including: abductor lever arm, femoral offset, femoral neck length, femoral neck-shaft angle, height of hip centre, body weight lever arm, acetabular version, and abductor angle. All hip measurements were taken from the ipsilateral side of the knee in interest. Each variable was then compared independently among the three groups via analysis of covariance (ANCOVA), controlling for age, sex, and body mass index (BMI), and followed up with a post-hoc Bonferroni analysis to distinguish pairwise group differences. Results. The ANCOVA analysis showed a significant difference in height of hip centre (p=0.001), femoral neck-shaft angle (p=0.009), and abductor angle (p=0.001). Compared to controls, knees with LOA had an increased height of hip centre (p=0.001) and knees with MOA had a decreased abductor angle (p=0.046). Compared to knees with MOA, those with LOA had a more valgus neck-shaft angle (p=0.007) and increased abductor angle (p=0.001). Conclusion. Our study demonstrates that variations in hip geometry that affect the moment-generating capacity of the hip abductors are associated with the presence and compartmental distribution of tibiofemoral OA in the ipsilateral knee. Anatomical arrangements that reduce the hip abductor moment arm are more strongly associated with LOA than with MOA

Summary Statement. OA knee with subchondral cyst formation presented differential microstructure and mechanical competence of trabecular bone. This finding sheds light on the pivot role of subchondral cyst in OA bone pathophysiology. Introduction. Subchondral bone cyst (SBC) is a major radiological finding in knee osteoarthritis (OA), together with joint space narrowing, osteophyte and sclerotic bone formation. There is mounting evidence showing that SBC originates in the same region as bone marrow lesions (BMLs). The presence of subchondral bone cyst (SBCs), in conjunction with BMLs, was associated with the severity of pain, and was able to predict tibial cartilage lolume loss and risk of joint replacement surgery in knee OA patient. It is speculated that the presence of SBCs might increase intraosseous pressure of subchondral bone, and trigger active remodeling and high turnover of surrounding trabecular bone. Yet the exact effect of SBC on the structural and mechanical properties trabecular bone, which provides the support to overlying articular cartilage, remains to be elucidated. Therefore, this study aimed to investiate the microstructure and mechanical competence of trabecular bone of knee OA in presence or absence of SBC. Patients & Methods. A total of 20 postmenopausal women (54–87 years old) with the late-stage of primary knee OA were recruited in this study. Tibial plateau specimens were collected during joint replacement surgery. The samples were grouped for comparison according to presence or absences of SBC in micro-CT images. For micro-CT examination, a cylindrical volume of region of interest (VOI) of 10mm in diameter and 1mm in height was used to cover the trabecular bone region surrounding SBC, and then a cubic VOI of 3.5×3.5×3.5mm. 3. was applied in different anatomic locations of tibial plateau, such as medial, intermediate and lateral part, for the analyses of trabecular bone microstructure. Subsequently, two cylinders of subchondral bone specimens were drilled for each sample with micro-CT guidance from lateral portion of cystic wall along the direction of physiological loading of knee joint. The specimens were processed for micro-CT and mechanical testing using MTS 858 Mini Bionix sequentially. Each specimen was compressed in a longitudinal direction at a speed of 1mm/minute; the ultimate strength and modulus of the specimens were generated. Comparisons of microstructure and mechanical properties of trabecular bone were performed between two groups using student t test. The structure-mechanics relationship was also investigated using Pearson correlation. Results. The bone volume fraction (BV/TV, %) was significantly higher in knee OA specimens in presence of SBC (32±7%) in comparison with those in absence of SBC (16±5%, p<0.001). Meanwhile there were more plate-like trabecular bone surrounding SBC (0.78±0.61) than those without SBC (1.81±0.28, p<0.001), which was indicated by structure model index (0∼3). Furthermore, the trend in conversion of rod-like (close to 3) towards plate-like trabeculae was noticed in different locations of knee OA specimens with SBC formation. Trabecular bone around SBC presented higher modulus (73±22MPa) compared with those without SBC (45±29MPa, p=0.034). The stiffer trabecular bone in presence of SBC correlated with its plate-like morphology (r=0.696, p<0.001) as well as bone volume fraction (r=0.578, p=0.004). Conclusion. Presence of SBC was associated with conversion of trabeculae towards plate-like morphology together with the increase of mechanical competence in advanced knee OA

Aim

Osteoarthritis (OA) is caused by complex interactions between genetic and environmental factors. Epigenetic mechanisms control the expression of genes and are likely to regulate the OA transcriptome. We performed integrative genomic analyses to define methylation-gene expression relationships in osteoarthritic cartilage.

Objectives

This study looked to analyse the expression levels of microRNA-140-3p and microRNA-140-5p in synovial fluid, and their correlations to the severity of disease regarding knee osteoarthritis (OA).

Objectives

To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.

Objectives

The purpose of this study was to compare the results and complications of tibial lengthening over an intramedullary nail with treatment using the traditional Ilizarov method.

Osteoarthritis (OA) is an important cause of pain, disability and economic loss in humans, and is similarly important in the horse. Recent knowledge on post-traumatic OA has suggested opportunities for early intervention, but it is difficult to identify the appropriate time of these interventions. The horse provides two useful mechanisms to answer these questions: 1) extensive experience with clinical OA in horses; and 2) use of a consistently predictable model of OA that can help study early pathobiological events, define targets for therapeutic intervention and then test these putative therapies. This paper summarises the syndromes of clinical OA in horses including pathogenesis, diagnosis and treatment, and details controlled studies of various treatment options using an equine model of clinical OA.