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Les prothèses totales de hanche (PTH) des patients très jeunes correspondent en règle aux prothèses posées chez des patients de moins de 30 à 35 ans. Elles représentent 3 % des opérés de moins de 55 ans et environ un pour cent de l'ensemble des opérés. L'étiologie menant à une PTH diffère de celles des patients plus âgés : on retrouve en effet moins de coxarthrose et plus de nécroses aseptiques et de pathologies inflammatoires. Au fil du temps, les implants non cimentés deviennent prédominants. Les couples métal-polyéthylène et surtout céramique-polyéthylène restent majoritaires mais les couples céramique-céramique sont de plus en plus employés. Chez les sujets jeunes, la PTH sera soumise à des contraintes plus intenses et sur une durée a priori très longue. Cependant, si les résultats des séries historiques montrent des taux de survie défavorables, les séries actuelles sont plus optimistes et montrent des taux de survie à moyen terme proches de ceux des séries tout âge confondu. Les résultats fonctionnels chez ces patients jeunes sont excellents quels que soient des scores utilisés. Total hip arthroplasty (THA) in very young people are those implanted in patients under 30 to 35 years old. They represent 3 % of the patients under 55 years of age and about one percent of all operated patients. The etiology leading to the arthroplasty is not the same as those of the older patients. Osteoarthritis is less frequent while avascular necrosis and inflammatory arthritis are more frequent. Over time, uncemented implants becomes predominant. Metal-polyethylene and mostly ceramic-polyethylene bearings remain predominant but ceramic-ceramic bearings are increasingly used. THA in young people will undergo more severe stress and are supposed to have a longer lifespan. Old clinical series show unfavorable survival rates. Nevertheless, recent series are more optimistic and show mid term results quite identical to that of all ages groups series. The functional results are excellent whatever the clinical scores may be. [ABSTRACT FROM AUTHOR]

Résumé: L’hallux valgus est une déviation latérale du gros orteil, correspondant à une angle métatarsophalangien de plus de 10°, qui survient le plus souvent chez la femme de plus de 40ans. C’est la douleur et la gêne au chaussage et à la marche qui motivent la consultation chirurgicale. De nombreuses techniques chirurgicales sont décrites et proposées, les plus récentes font appel à la chirurgie mini-invasive voire percutanée. L’hallux rigidus est une arthrose de la 1re articulation métatarsophalangienne sans déviation d’axe, qui se manifeste avant tout par des douleurs associées à terme à une raideur plus ou moins importante. Lorsque l’arthrose n’est pas trop sévère, le traitement chirurgical comporte une résection des ostéophytes et une ostéotomie décompressive selon l’analyse morphologique du premier rayon. Sinon l’arthrodèse reste de mise. Les sésamoïdopathies correspondent à plusieurs pathologies qui s’expriment par une douleur localisée d’évolution extrêmement longue. Le traitement en est avant tout conservateur. [Copyright &y& Elsevier]

Purpose: In the over-80 s, femoral bone is often osteoporotic and unlikely to be conducive to periprosthetic bone rehabitation. This observation often leads to cemented fixation for hemiarthroplasty in femoral neck fracture. Hydroxyapatite is a bioactive coating that has already demonstrated its osteoinductive properties. Our hypothesis is that hydroxyapatite enables prosthetic osseointegration in patients over 80, as well as periprosthetic cortical thickening. The objective was to evaluate the osseointegration of a hydroxyapatite-coated femoral stem in femoral neck fractures in the over-80 s, and the evaluation of the periprosthetic bone regeneration permitted by hydroxyapatite. Methods: This was a retrospective study. Osseointegration and periprosthetic bone regeneration were assessed on pre-operative, immediate post-operative and last follow-up radiographs with Engh score, O-SS score, cortical index, Canal Bone Ration (CBR) and Canal Fill Ratio (CFR). Results: One hundred and forty-six patients were included. At last follow-up, 99.3% (n = 145) of stems were osseointegrated. The mean Engh score was 19.9 [SD 3.1]. The mean O-SS score was 19.1 [SD 2.4], corresponding to very good osseointegration. The mean CBR at last follow-up was 0.48 [SD 0.07], corresponding to a non-osteoporotic femur. There was a significant difference with pre-operative CBR (p < 0,001). The pre-operative cortical index and the index at the last follow-up were significantly different for all levels of measurement (p < 0,001). The CFR at last follow-up was also significantly different with the post-operative CFR (p < 0,001). Conclusion: This study shows the value of using a hydroxyapatite-coated stem on senile, osteoporotic bone to improve cortical thickness along the entire length of femoral bone. [ABSTRACT FROM AUTHOR]

Introduction L’instabilité du genou, liée à une lésion du ligament croisé antérieur, est traitée par reconstruction chirurgicale. Pendant la période de transformation histologique du transplant devenant néo-ligament, la privation d’informations proprioceptives musculo-tendino-articulaires est importante. Cette étude en cours vise à comparer les bénéfices d’un protocole de rééducation innovant (prise en charge [PEC] à sec, PEC en milieu aquatique) à ceux d’un protocole de rééducation conventionnelle (recommandations Haute autorité de Santé 2008) en termes de cinétique de récupération et de développement des compétences proprioceptives des sportifs opérés d’une ligamentoplastie du genou. Matériel et méthodes À ce jour, 76 patients ont été répartis en deux groupes de rééducation (randomisation) ; ainsi, 40 patients ont suivi un protocole de rééducation conventionnelle (Gr 1) et 36 un protocole associant une rééducation conventionnelle à durée réduite avec une rééducation en milieu aquatique (Gr 2). La durée totale de PEC était identique dans les deux groupes. Un bilan posturographique a permis d’évaluer la qualité du contrôle postural avant intervention chirurgicale (E1), puis 15 jours (E2, début de la rééducation propre au protocole de recherche), 1 mois (E3, fin de la rééducation propre au protocole de recherche), 2 mois (E4) et 6 mois (E5) après intervention chirurgicale. L’intensité de la douleur a également été évaluée (échelle EVA). Résultats Une amélioration du contrôle postural est observée entre E2 et E3 dans les deux groupes ( p < 0,05). Une diminution de la douleur dans les deux groupes entre E2 et E3 ( p < 0,05) et dans le Gr2 entre E4 et E5 ( p < 0,05) est observée. Discussion–conclusion Concernant l’analyse transversale pour la comparaison entre les deux groupes, il est nécessaire d’inclure l’effectif initialement déterminé sur le plan statistique, c’est-à-dire 128 patients afin d’évaluer l’efficacité d’un programme de rééducation innovant sur un retour aux activités sociales, sportives et professionnelles plus précoce. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Chondrocytes hypertrophy is a physiological process observed in endochondral ossification during development until adolescence in human. It can also be observed during pathophysiological conditions such as osteoarthritis. Hypertrophic chondrocytes synthesise collagen X and express matrix metalloproteinase 13 and alkaline phosphatase. The cellular models available to study this process are either not convenient, they might lead to a rapid dedifferentiation of chondrocytes, or they are far from the physiological conditions. The objective of this study was to design an user-friendly 2D-primary cell culture of young articular chondrocytes of rat able to follow the terminal differentiation process.EXPERIMENTAL DESIGN: After confluence, chondrocytes were cultured according to 4 differentiation protocols. Protocol 1 contained DMEM/F12 supplemented with 10% foetal bovine serum (FBS) and 2 μg/ml insulin. Protocol 2 contained alpha-MEM supplemented with 5% FBS and 2 μg/ml insulin. Protocol 3 contained 2% FBS and 2 μg/ml insulin. Protocol 4 contained DMEM/F12 supplemented with 2% FBS in absence or in presence of 2 μg/ml insulin and 37.5 μg/ml ascorbate. The cell morphology was observed by phase-contrast microscopy and the expression of markers specific of mature and hypertrophic chondrocytes were assessed by RT-qPCR.RESULTS: The effect of a decrease in nutrient quality of the culture medium after confluence was tested using protocols 1, 2 and 3. Protocol 1 did not allow the maintenance of chondrocyte phenotype more than one week, because cells became fibroblastic. A decrease in Sox9 mRNA expression, in collagen II/collagen I and in aggrecan/versican mRNA ratios was also found with protocol 1. Protocol 3 was the best when compared with protocols 1 and 2. It allowed chondrocytes to adopt a hypertrophic morphology. Cells also expressed the collagen X specific hypertrophic marker, and presented an increase in collagen II/I and aggrecan/versican ratios after 15 days of culture post-confluence. The effect of the insulin/ascorbate supplementation was studied using protocol 4. The insulin/ascorbate supplementation allowed an earlier chondrocytes conversion to terminal differentiation with a prolonged effect till 3 weeks post-confluence, compared to control without insulin/ascorbate. Finally, the profile of chondrocyte differentiation was checked during 5 successive sub-cultures. Only the first passage could be used to study hypertrophy.CONCLUSION: A convenient protocol to study chondrocyte hypertrophy is proposed. Protocol 4 offers the possibility to study this differentiation phenotype which is crucial for the development of articular diseases such as osteoarthritis. Our model could also be used in tissue engineering for cartilage repair strategies in which hypertrophic differentiation of chondrocyte should be avoided. [ABSTRACT FROM AUTHOR]

While mesenchymal stem cells represent an interesting cell source for regenerative medicine, several points have to be investigated to improve their use in clinical, and in particular in the elderly population. This work studied the proliferation capacity of mesenchymal stem cells isolated from human bone marrow in function of donor's age. Doubling time after in vitro culture, clonogenicity and phenotype were analyzed in 17 samples ranging from 3 to 85 years old (mean 47±27). Results showed an increase in the doubling time for cell coming from old donor compared to cells coming from young ones. This was accompanied by a decrease in clonogenicity while no changes were observe in cell phenotype. In conclusion, this study showed an effect of donor's age on the proliferation capacity of mesenchymal stem cells isolated from bone marrow that was correlated to a decrease in clonogenicity. The comprehension of molecular mechanism involved in this process could help to improve the clinical application of mesenchymal stem cells. [ABSTRACT FROM AUTHOR]

Purpose: After previous results observed with a generic health-related quality of life (HRQoL) instrument, we aimed to confirm that immediate postoperative patient satisfaction with care predicts self-perceived health 1 year after total hip replacement/total knee replacement (THR/TKR), using an osteoarthritis (OA)-specific HRQoL questionnaire. Methods: This was a French multicenter prospective cohort study of patients after THR/TKR. HRQoL was assessed by the OsteoArthritis Knee and Hip Quality Of Life (OAKHQOL) instrument before and after surgery and satisfaction with care by the Quality of Care Scale (QCS). Results: A total of 189 patients were followed up 12 months after discharge (mean age 68.9 SD = 8.5; 41.9% male). After adjustment for relevant variables, patients satisfied with care postoperatively showed greater 1-year postoperative HRQOL than those less satisfied with care. Patients satisfied with medical information had a higher postoperative HRQoL score than patients less satisfied in 3 of 5 OAKHQOL dimensions ( P < 0.001 to P = 0.02), and patients satisfied with relationships with staff and daily routine scored higher on all HRQoL dimensions than did less-satisfied patients (all P < 0.001). Conclusions: These new findings with an OA-specific HRQOL questionnaire confirm that immediate postoperative satisfaction with care after THR/TKR for OA is a good predictor of self-perceived health status 1 year after surgery. Satisfaction with care therefore represents a relevant indicator of patient-reported health and is quickly accessible to clinicians. [ABSTRACT FROM AUTHOR]

The article discusses topics which were discussed at a round table discussion of the TALUS group which was held during a January 2011 annual meeting of the Group for Study of Osteoarticular Surgery. Topics included ankle sprains, fibular pathology and tarsal synostosis. The event was attended by several orthopaedic professionals including Michel Benichou, Ali Ghorbani and Pascal Faure.

Objectives: To establish recommendations for pharmacological treatment of knee osteoarthritis specific to France.Methods: On behalf of the French Society of Rheumatology (SFR), a bibliography group analyzed the literature on the efficacy and safety of each pharmacological treatment for knee osteoarthritis. This group joined a multidisciplinary working group to draw up recommendations. Strength of recommendation and quality of evidence level were assigned to each recommendation. A review committee gave its level of agreement.Results: Five general principles were established: 1) need to combine pharmacological and non-pharmacological treatments, 2) personalization of treatment, 3) symptomatic and/or functional aim of pharmacological treatments, 4) need to regularly re-assess the treatments and 5) discussion about arthroplasty if medical treatment fails. Six recommendations involved oral treatments: 1) paracetamol should not necessarily be prescribed systematically and/or continuously, 2) NSAIDs, possibly as first-line, 3) weak opioids, 4) strong opioids, 5) symptomatic slow-acting drugs of osteoarthritis, and 6) duloxetine (off-label use). Two recommendations involved topical agents (NSAIDs and capsaicin<1%). Three recommendations involved intra-articular treatments: corticosteroid or hyaluronic acid injections that can be proposed to patients. The experts did not draw a conclusion about the benefits of platelet-rich plasma injections.Conclusion: These are the first recommendations of the SFR on the pharmacological treatment of knee osteoarthritis. [ABSTRACT FROM AUTHOR]

Établir sous l'égide de la Société française de rhumatologie (SFR) des recommandations sur les traitements pharmacologiques de la gonarthrose. Le groupe de bibliographie a réalisé une analyse de la littérature sur l'efficacité et la tolérance de chaque traitement. Ce groupe a rejoint un groupe de travail pluridisciplinaire pour élaborer les recommandations par vote et recueil du niveau d'accord. Chaque recommandation a fait l'objet d'une force de recommandation et d'un niveau d'évidence. Un groupe de lecture a donné son niveau d'agrément. Cinq principes généraux ont été émis sur : (1) la nécessité de combiner traitements pharmacologiques et non pharmacologiques, (2) la personnalisation de la prise en charge, (3) l'objectif symptomatique et/ou fonctionnel des traitements pharmacologiques, (4) la nécessité d'une réévaluation médicale régulière des traitements et (5) la discussion d'une arthroplastie en cas d'échec du traitement médical. Six recommandations ont concerné les traitements oraux : (1) le paracétamol qui ne doit pas nécessairement être prescrit de manière systématique et/ou continue, (2) les AINS, éventuellement en 1re intention, (3) les opioïdes faibles, (4) les opioïdes forts et (5) les anti-arthrosiques symptomatiques d'action lente et, (6) hors AMM, la duloxétine. Deux recommandations ont concerné les topiques (AINS et capsaïcine < 1 %). Trois recommandations ont concerné les traitements intra-articulaires : les injections de corticoïdes ou d'acide hyaluronique qui peuvent être proposés. Les experts n'ont pas statué sur l'intérêt des injections de plasma riche en plaquettes. Il s'agit des 1res recommandations de la SFR sur la prise en charge pharmacologique de la gonarthrose. [ABSTRACT FROM AUTHOR]

Background: MSCs isolated from bone marrow (BM-MSCs) have well-established chondrogenic potential, but MSCs derived from the synovial membrane (SM-MSCs) and synovial fluid (SF-MSCs) are thought to possess superior chondrogenicity. This study aimed to compare the in vitro immunophenotype and trilineage and chondrogenic potential of BM-MSCs to SM-MSCs and SF-MSCs. Methods: MSCs were isolated from bone marrow (BM-MSCs), synovial membrane (SM-MSCs), and synovial fluid (SF-MSCs) extracted from the hips (BM) and knees (SM and SF) of advanced OA patients undergoing arthroplasty. Flow cytometric analysis was used at P2 to evaluate cell stemness. The trilinear differentiation test was performed at P2. At P3, MSC-seeded collagen sponges were cultured in chondrogenic medium for 28 days. Chondrogenic gene expression was quantified by qRT-PCR. Finally, the implants were stained to assess the deposition of proteoglycans and type II collagen. Results: Despite variability, the immunophenotyping of BM-MSCs, SM-MSCs, and SF-MSCs was quite similar. All cell types were positive for the expression of stem cell markers and negative for exclusion markers. Additionally, chondrogenic differentiation and hypertrophy were more pronounced in BM-MSCs (ACAN, SOX9, COL2B, and COL10A) than in SF-MSCs, with SM-MSCs having intermediate characteristics. Concerning matrix synthesis, the three cell types were equipotent in terms of GAG content, while BM-MSC ECM synthesis of type II collagen was superior. Conclusions: Chondrogenic MSCs are easily collected from SM and SF in advanced human OA, but in vitro chondrogenesis that is superior to age-matched BM-MSCs should not be expected. However, due to intra-articular priming, SF-MSCs did not overexpress hypertrophic gene. [ABSTRACT FROM AUTHOR]

3D bioprinting offers interesting opportunities for 3D tissue printing by providing living cells with appropriate scaffolds with a dedicated structure. Biological advances in bioinks are currently promising for cell encapsulation, particularly that of mesenchymal stem cells (MSCs). We present herein the development of cartilage implants by 3D bioprinting that deliver MSCs encapsulated in an original bioink at low concentration. 3D-bioprinted constructs (10 × 10 × 4 mm) were printed using alginate/gelatin/fibrinogen bioink mixed with human bone marrow MSCs. The influence of the bioprinting process and chondrogenic differentiation on MSC metabolism, gene profiles, and extracellular matrix (ECM) production at two different MSC concentrations (1 million or 2 million cells/mL) was assessed on day 28 (D28) by using MTT tests, real-time RT-PCR, and histology and immunohistochemistry, respectively. Then, the effect of the environment (growth factors such as TGF-β1/3 and/or BMP2 and oxygen tension) on chondrogenicity was evaluated at a 1 M cell/mL concentration on D28 and D56 by measuring mitochondrial activity, chondrogenic gene expression, and the quality of cartilaginous matrix synthesis. We confirmed the safety of bioextrusion and gelation at concentrations of 1 million and 2 million MSC/mL in terms of cellular metabolism. The chondrogenic effect of TGF-β1 was verified within the substitute on D28 by measuring chondrogenic gene expression and ECM synthesis (glycosaminoglycans and type II collagen) on D28. The 1 M concentration represented the best compromise. We then evaluated the influence of various environmental factors on the substitutes on D28 (differentiation) and D56 (synthesis). Chondrogenic gene expression was maximal on D28 under the influence of TGF-β1 or TGF-β3 either alone or in combination with BMP-2. Hypoxia suppressed the expression of hypertrophic and osteogenic genes. ECM synthesis was maximal on D56 for both glycosaminoglycans and type II collagen, particularly in the presence of a combination of TGF-β1 and BMP-2. Continuous hypoxia did not influence matrix synthesis but significantly reduced the appearance of microcalcifications within the extracellular matrix. The described strategy is very promising for 3D bioprinting by the bioextrusion of an original bioink containing a low concentration of MSCs followed by the culture of the substitutes in hypoxic conditions under the combined influence of TGF-β1 and BMP-2. [ABSTRACT FROM AUTHOR]

In tissue engineering approaches, the quality of substitutes is a key element to determine its ability to treat cartilage defects. However, in clinical practice, the evaluation of tissue-engineered cartilage substitute quality is not possible due to the invasiveness of the standard procedure, which is to date histology. The aim of this work was to validate a new innovative system performed from two-photon excitation laser adapted to an optical macroscope to evaluate at macroscopic scale the collagen network in cartilage tissue-engineered substitutes in confrontation with gold standard histologic techniques or immunohistochemistry to visualize type II collagen. This system permitted to differentiate the quality of collagen network between ITS and TGF-β1 treatments. Multiscale large field imaging combined to multimodality approaches (SHG-TCSPC) at macroscopical scale represent an innovative and non-invasive technique to monitor the quality of collagen network in cartilage tissue-engineered substitutes before in vivo implantation. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the displacements of center of pressure (COP) using an in-shoe recording system (F-Scan) before and after motor nerve block and neurotomy of the tibial nerve in spastic equinovarus foot. Thirty-nine patients (age 45 +/- 15 yr) underwent a motor nerve block; 16 (age 38 +/- 15.2 yr) had tibial neurotomy, combined with tendinous surgery (n = 9). The displacement of the COP (anteropos-terior [AP], lateral deviation [LD], posterior margin [PM]) was compared between paretic and nonparetic limbs before and after block and surgery. At baseline, the nonparetic limb had a higher AP (17.3 vs 12.3 cm,p < 0.001) and LD (4.0 vs 3.3 cm, p = 0.001) and a smaller PM (2.9 vs 4.7 cm,p = 0.001). For the paretic limb, a significant increase of AP was observed after block (13.5 vs 12.3 cm, p = 0.02) and after surgery (13.7 vs 12.3 cm, p = 0.03). A significant decrease of PM was observed after surgery (4.5 vs 3.3 cm, p < 0.001) with no more difference between two limbs (2.8 vs 3.3 cm, p = 0.44). This study shows that the F-Scan system can be used to quantify impairments and be useful to evaluate the effects of treatment for spastic foot. It suggests that changes in AP displacement following block may predict the effects of neurotomy. [ABSTRACT FROM AUTHOR]

Introduction: There are multiple surgical treatment methods for proximal humerus fractures (PHF), but rarely do they provide satisfactory results. The objective of this study was to assess radioclinical outcomes and complications in patients treated using a modern intramedullary nailing system the Telegraph IV. Materials and methods: This is an observational multicenter study cohort conducted between March 2008 and December 2009 on 105 patients admitted with a diagnosis of PHF and operated on two trauma I centers. The Neer and Articular Surgical neck Tuberosities classifications were used for the study. The primary outcome measure was the clinical Constant score. Follow-up of the patients was done at 6 weeks, 3 months, 6 months, 1 year, and 3 years after the procedure. Results: A total of 67 patients (51 women and 16 men) were assessed at a mean of 38 months. The weighted Constant score was 88 %. The mean rate of complications was 16 %. The weighted Constant scores were 84 and 95 % for the 2- and 3-part groups, respectively. Articular 4-part fractures had an average score of 86 % when they were valgus impacted and 67 % for complex disengaged fractures. Notably, the complication rate was 67 % for this latter group. Conclusions: Our clinical results support the use of this antegrade nailing for extra-articular and valgus-impacted articular fractures. This procedure does not appear suitable for displaced articular fracture for which arthroplasty may be indicated by elderly. [ABSTRACT FROM AUTHOR]

Proteomics users enjoy the rapid development of LC-MS-based label-free relative quantification methods but in practice these remain restricted to mass spectrometers using electrospray ionization. Here, tools dedicated to ion chromatogram extraction, time alignment, signal normalization and statistical analysis were used to interpret label-free relative difference between primary human chondrocyte secretomes and dilutions thereof, analyzed successively by LC-MALDI. The analysis of secretomes diluted into culture medium demonstrated that abundant proteins could be relatively quantified within 1.5–20-fold changes with satisfactory statistics. In addition, comparison of multiple samples requires analyzing most samples in TOF mode only, saving considerable machine-time usage. The method allowed identification and quantification of most secreted proteins relevant to the chondrocyte phenotype and evidenced their up- or down regulations by TGFβ1 and patient-to-patient differential expression. Novel targets of TGFβ1 were evidenced, such as pro-collagen C-proteinase enhancer protein 1, Metalloproteinase inhibitor 1, Fibulin-3, Tetranectin and Cartilage Intermediate Layer Protein 1, while others match previous findings. Several were verified by Western blot. This whole workflow is non-invasive, compatible with many cell culture protocols, technically straightforward and rapid, particularly regarding mass spectrometer time usage and could make label-free LC-MALDI analysis of low-complexity proteomes a major tool for routine cell culture characterization. Biological significance The present work presents the adaptation of label free relative protein quantification principles to LC-MALDI data to rapidly measure protein fold-changes between samples of relative complexity and its utility to characterize the secreted proteome of human primary chondrocytes. The method was employed to characterize the chondrocyte secretome regulation by TGFβ1 and is proposed as a routine tool to assess the quality of biomaterials designed for cartilage repair and to quantitatively investigate the influence of environmental factors upon it. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Few studies have tried to discriminate a differential behavior between osteoarthritic (OA) osteoblasts (Obs). Based on osteocalcin level, we aimed, in the present study, to evaluate the capacity of OA Obs for producing molecules of the Wnt/β-catenin signaling pathway.METHODS: Human primary OA Obs (n=11) were exposed or not to 50 nM of 1,25 dihydroxyvitamin D3 (VitD3) for 24 h. Osteocalcin (OCN), TGF-β1, Dickkopf-related protein 2 (DKK2), R-spondin 2 (Rspo2), Wnt5b, and low density lipoprotein related-receptor 1 (LRP1) were evaluated by real time RT-PCR.RESULTS: All samples responded to VitD3 as validated by the increase in OCN expression. However two populations of Obs were discriminated; one called 'high responders' whose OCN stimulation was higher than 100 fold (mean 881 fold, p<0.01, n=5) and the second one whose stimulation was inferior to 100 fold (mean 47 fold, p<0.01, n=6), namely 'low responders'. In fact, high responders have a weaker basal expression of OCN. With regards to these two cell populations and in absence of VitD3 challenge, the expression level of TGF-β1 (15 fold, p<0.001), DKK2 (2.5 fold, p<0.002) and Wnt5b (5.5 fold, p<0.003) was higher in 'high responders', meanwhile Rspo2 and LRP1 expression was unchanged. VitD3 exacerbated this pattern but corrected OCN expression and favored Wnt agonist expression.CONCLUSION: We identified 2 populations of OA Obs according to the OCN expression under the control of VitD3. In addition under basal conditions, these 2 populations expressed differently TGF-β1, Wnt5b, DKK2, suggesting a heterogeneous differentiation and phenotype in Obs among OA patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: Non-union of long bones is still a current problem in traumatology. Although corticocancellous bone autograft remains the usual procedure for the treatment of non-union, innovative therapies such as, percutaneous autologous concentrated bone marrow grafting (PABMG), are now appearing.MATERIAL AND METHODS: Over a period of 8 years, 45 non-union of long bones were treated by PABMG in the Department of Orthopaedic and Traumatologic Surgery (University Hospital of Nancy, France): 26 tibiae, 16 femurs, 3 humeri. Efficiency was evaluated by clinical criteria: full weight-bearing without pain, absence of motion at non-union site, and radiological criteria: healing of 3 corticales out of 4.RESULTS: Eighteen out of 28 non-unions at the tibia were healed (69%), 10 at the femur (63%), but none was noticed at the humerus. Some pejorative prognosis factors were noted such as: tobacco, alcohol abuse, diabetes and history of infection at the fracture site. An earlier grafting improved the success rate. The number of CFU-F (Colony Forming Unit Fibroblastic) affected the healing time more than the healing rate.CONCLUSION: The procedure, even though a little invasive, enables the healing of non-union in two out of three cases with less morbidity than conventional procedures. This procedure fits perfectly into the therapeutic arsenal of non-union. [ABSTRACT FROM AUTHOR]

The role of body weight in the pathogenesis of osteoarthritis (OA) - previously considered the sole factor in the association between obesity and OA - is being re-evaluated as the contribution of adiposity to the cartilage degenerative process becomes clearer. The current study has been undertaken to better understand the role of adipose-derived proteins, namely adipokines, in OA. For this purpose, we investigated in patients with OA the relationships between the joint levels of leptin, adiponectin and resistin and those of factors involved in inflammation and cartilage maintenance. The sandwich enzyme-linked immunosorbent assays were used to determine in the synovial fluid (SF) from 35 OA patients, the concentrations of adipokines, interleukin-6 (IL-6) and transforming growth factor-β (TGF-β). The soluble form of leptin receptor (sOb-R) was also examined to evaluate the biological active free form of leptin. Correlation analysis indicate that IL-6 levels are positively related to the levels of resistin and adiponectin. Surprisingly, the free form of leptin, but not the total leptin, is negatively associated with IL-6. Beside, adiponectin is the single adipokine that is correlated with TGF-β. Interestingly, a sexual dimorphism is observed in the study as correlations between adipokines and IL-6 or TGF-β are found only with female OA patients. Taken together, these findings suggest that only adiponectin may contribute to the metabolic changes associated with OA. The three adipokines may also be involved in inflammation, but with opposite effects. Both resistin and adiponectin may exhibit pro-inflammatory activity while the free form of leptin may down-regulate the inflammation. [ABSTRACT FROM AUTHOR]

Background: Initially considered as an established salvage procedure for tibiotalocalcaneal arthrodesis (TTCA), intramedullary nailing indications have expanded as evidenced in recent literature. We have tried to identify factors influencing functional result and bone union. Methods: In a retrospective study, 30 patients were treated by a TTCA between January 2006 and November 2011. Indications, operative technique, bone fusion, X-rays and functional result [American Foot and Ankle Society (AOFAS) and short-form health survey (SF-36) scores] before and after surgery were registered and analyzed. Results: Thirty cases of TTCA were included. The patient's average age was 52 (range 24-90). Union rate was 86 % for the tibiotalar joint and 74 % for the subtalar joint with an average follow-up of 25.4 months (8-67). The mean AOFAS' score significantly improved (from 37 to 59) as the SF-36' score. Global complication rate was about 56 %. It has not been possible to identify factors significantly influencing bone fusion or functional results. All septic cases achieved fusion without any septic resurgence. Conclusion: Retrograde intramedullary nailing in TTCA is an effective technique, which allows good clinical results even in case of septic history of the patient. Fusion rate and functional results were not significantly influenced by any of the factors examined in this study. [ABSTRACT FROM AUTHOR]

Abstract: Chondrocalcin is among the most highly synthesized polypeptides in cartilage. This protein is released from its parent molecule, type II pro-collagen, after secretion by chondrocytes. A participation of extracellular, isolated chondrocalcin in mineralization was proposed more than 25years ago, but never demonstrated. Here, exogenous chondrocalcin was found to trigger MMP13 secretion and cartilage destruction ex vivo in human cartilage explants and did so by modulating the expression of interleukin-1β in primary chondrocyte cultures in vitro. Chondrocalcin was found internalized by chondrocytes. Uptake was found mediated by a single 18-mer peptide of chondrocalcin, which does not exhibit homology to any known cell-penetrating peptide. The isolated peptide, when artificially linked as a tetramer, inhibited gene expression regulation by chondrocalcin, suggesting a functional link between uptake and gene expression regulation. At the same time, the tetrameric peptide potentiated chondrocalcin uptake by chondrocytes, suggesting a cooperative mechanism of entry. The corresponding peptide from type I pro-collagen supported identical cell-penetration, suggesting that this property may be conserved among C-propeptides of fibrillar pro-collagens. Structural modeling localized this peptide to the tips of procollagen C-propeptide trimers. Our findings shed light on unexpected function and mechanism of action of these highly expressed proteins from vertebrates. [Copyright &y& Elsevier]

Aim. To determine whether viscosupplementation with intra-articular (i.a.) low- or high-molecular-weight hyaluronate (HA) injections influenced both chondral and synovial lesions in rats with surgically-induced OA knee. Methods. On D0, rats underwent anterior cruciate ligament transection (ACLX) and were divided in 4 groups: sham group, ACLX-saline control group, ACLX-hyaluronate group, ACLX-hylan group. IA injections were performed on D7, D14 and D21. Histological grading of chondral and synovial lesions were performed on D28. Concomitant immunostainings of Caspase3a and Hsp70 were also performed. Results. Articular damages were significantly reduced in both HAs-treated knee joints. In contrast, a significant increase of histological score of synovial inflammation was noted in both ACLX + HAs groups. Apoptotic events significantly decreased as anti-apoptotic Hsp70 expression increased significantly in both HAs groups. Conclusion. HAs may exert, independently of its molecular weight, ambivalent properties on articular structures, simultaneously exerting chondroprotective properties and promoting long-term subacute synovitis. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are regarded as a potential autologous source for cartilage repair, because they can differentiate into chondrocytes by transforming growth factor-beta (TGF-β) treatment under the 3-dimensional (3-D) culture condition. In addition to these molecular and biochemical methods, the mechanical regulation of differentiation and matrix formation by MSCs is only starting to be considered. Recently, mechanical loading has been shown to induce chondrogenesis of MSCs in vitro. In this study, we investigated the effects of a calibrated agitation on the chondrogenesis of human bone MSCs (MSCs) in a 3-D alginate culture (day 28) and on the maintenance of chondrogenic phenotypes. Biomechanical stimulation of MSCs increased: (i) types 1 and 2 collagen formation; (ii) the expression of chondrogenic markers such as COMP and SOX9; and (iii) the capacity to maintain the chondrogenic phenotypes. Notably, these effects were shown without TGF-β treatment. These results suggest that a mechanical stimulation could be an efficient method to induce chondrogenic differentiation of MSCs in vitro for cartilage tissue engineering in a 3-D environment. Additionally, it appears that MSCs and chondrocyte responses to mechanical stimulation are not identical. [ABSTRACT FROM AUTHOR]

Abstract: The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes. In the past, MATN3 was found required for cartilage homeostasis, but also involved in osteoarthritis-related pro-catabolic functions. Here, to better understand the pathological and physiological functions of MATN3, its concentration as a circulating protein in articular fluids of human osteoarthritic patients was determined and its functions as a recombinant protein produced in human cells were investigated with particular emphasis on the physical state under which it is presented to chondrocytes. MATN3 down-regulated cartilage extracellular matrix (ECM) synthesis and up-regulated catabolism when administered as a soluble protein. When artificially immobilized, however, MATN3 induced chondrocyte adhesion via a α5β1 integrin-dependent mechanism, AKT activation and favored survival and ECM synthesis. Furthermore, MATN3 bound directly to isolated α5β1 integrin in vitro. TGFβ1 stimulation of chondrocytes allowed integration of exogenous MATN3 into their ECM and ECM-integrated MATN3 induced AKT phosphorylation and improved ECM synthesis and accumulation. In conclusion, the integration of MATN3 to the pericellular matrix of chondrocytes critically determines the direction toward which MATN3 regulates cartilage metabolism. These data explain how MATN3 plays either beneficial or detrimental functions in cartilage and highlight the important role played by the physical state of ECM molecules. [Copyright &y& Elsevier]

Loss of glycosaminoglycan (GAG) chains of proteoglycans (PGs) is an early event of osteoarthritis (OA) resulting in cartilage degradation that has been previously demonstrated in both huma and experimental OA models. However, the mechanism of GAG loss and the role of xylosyltransferase-I (XT-I) that initiates GAG biosynthesis onto PG molecules in the pathogenic process of human OA are unknown. In this study, we have characterized XT-I expression and activity together with GAG synthesis in human OA cartilage obtained from different regions of the same joint, defined as "normal", "late-stage" or adjacent to "late-stage". The results showed that GAG synthesis and content increased in cartilage from areas flanking OA lesions compared to cartilage from macroscopically "normal" unaffected regions, while decreased in "late-stage" OA cartilage lesions. This increase in anabolic state was associated with a marked upregulation of XT-I expression and activity in cartilage "next to lesion" while a decrease in the "late-stage" OA cartilage. Importantly, XT-I inhibition by shRNA or forcedexpression with a pCMV-XT-I construct correlated with the modulation of GAG anabolism in human cartilage explants. The observation that XT-I gene expression was down-regulated by IL-1b and up-regulated by TGF-b1 indicates that these cytokines may play a role in regulating GAG content in human OA. Noteworthy, expression of IL-1b receptor (IL-1R1) was down-regulated whereas that of TGF-b1 was up-regulated in early OA cartilage. Theses observations may account for upregulation of XT-I and sustained GAG synthesis prior to the development of cartilage lesions during the pathogenic process of OA. [ABSTRACT FROM AUTHOR]

Tissue engineering aims at developing functional substitutes for damaged tissues by mimicking natural tissues. In particular, tissue engineering for bone regeneration enables healing of some bone diseases. Thus, several methods have been developed in order to produce implantable biomaterial structures that imitate the constitution of bone. Electrospinning is one of these methods. This technique produces nonwoven scaffolds made of nanofibers which size and organization match those of the extracellular matrix. Until now, seldom electrospun scaffolds were produced with thickness exceeding one millimeter. This article introduces a new kind of electrospun membrane called 3D scaffold of thickness easily exceeding one centimeter. The manufacturing involves a solution of poly(ℇ-caprolactone) in DMF/DCM system. The aim is to establish parameters for electrospinning in order to characterize these 3D scaffolds and, establish whether such scaffolds are potentially interesting for bone regeneration. [ABSTRACT FROM AUTHOR]

Although extensive evidence support the key role of adipokines in cartilage homeostasis, contradictory data have been found for their expression and their effects in chondrocytes. This study was then undertaken to determine whether a phenotypic modulation may affect the expression of adipokines and their receptors in human chondrocytes. The expression of leptin, adiponectin and their receptors, as well as cartilage-specific genes was examined in chondrocytes obtained from patients with osteoarthritis either directly after cells harvest or after culture in monolayer or in alginate beads. The results showed major changes in the gene expression pattern after culture in monolayer with a shift from the adipokines to their receptors. Interestingly, this downregulation of adipokines was associated with a loss of chondrocyte phenotype, and chondrocytes recovered a cartilage-like expression profile of leptin and adiponectin when cultured in a tridimensional chondrocyte phenotype-inducing system, but ceased expressing their receptors. Further experiments clearly showed that leptin but not adiponectin promoted the expression of cartilage-specific markers through mitogen-activated protein kinase, Janus kinase and phosphatidylinositol-3 kinase signaling pathways. In conclusion, our data indicate that any phenotypic modulation could affect chondrocyte responsiveness to leptin or adiponectin, and provide evidence for an important role for leptin in regulating the expression of cartilage-specific markers. J. Cell. Physiol. 226: 2790-2797, 2011. © 2011 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we presented a new type of coating based on polyelectrolyte multilayers containing sequentially adsorbed active shRNA calcium phosphate nanoparticles for locally defined and temporarily variable gene silencing. Therefore, we investigated multi-shell calcium phosphate-shRNA nanoparticles embedded into a polyelectrolyte multilayer for gene silencing. As model system, we synthesized triple-shell calcium phosphate-shRNA nanoparticles (NP) and prepared polyelectrolyte multilayers films made of nanoparticles and poly-(l-lysine) (PLL). The biological activities of these polyelectrolyte multilayers films were tested by the production of osteopontin and osteocalcin in the human osteoblasts (HOb) which were cultivated on the PEM films. This new strategy can be used to efficiently control the bone formation and could be applicable in tissue engineering. [Copyright &y& Elsevier]

Abstract: This study aimed to evaluate the role of the knee joint in the neurosensory organization of balance control and the generation of postural sensorimotor strategies. Ten patients, aged over 60 years and having undergone unilateral total knee replacement (TKR) for osteoarthritis, and 20 controls were submitted to static and dynamic posturographic tests and to a sensory organization test (SOT) aiming at evaluating postural control in quiet stance and during movement. The patients were submitted to these evaluations after the disappearance of pain (TKR1) and at the end of a 6-week rehabilitation program (TKR2). Balance control being greatly improved at TKR2 compared to TKR1, the patients attain a quality of postural regulation similar to that of the controls; some postural abnormalities did however persist for the static test. Moreover, SOT values at TKR2 close to those of the controls highlighted an improvement in motor response, better management in altered proprioceptive information situations, and greater use of the ankle to control balance. This model of intervention on the knee joint, namely knee replacement due to osteoarthritis, has shown that gradual functional sensorimotor restoration after TKR, due to intrasensory proprioceptive compensation either at knee, or at other joint levels (hip/ankle), improves dynamic balance control. This reacquisition allows the knee joint to recover its corrective compensatory role in postural regulation allowing, through neuroplasticity, the modification of muscular activation sequences and, thus, the implementation of anticipatory sensorimotor strategies. [Copyright &y& Elsevier]

This study investigated the gene expression profile of human mesenchymal stem cells seeded in collagen sponge for 28 days in three different mediums: (1) basal medium as control containing ITS alone, (2) ITS+TGF-β1 alone or (3) ITS 1% supplemented sequentially by TGF-β1 (D3-D14) followed by BMP-2 (D15-D28). Differential expression of 84 genes implicated in chondrogenic and osteogenic differentiation of MSCs was analyzed at D28 by real-time RT-PCR array technology. TGF-β1 alone down-regulated two genes, CD36 and cathepsin K. Sixteen genes were significantly up-regulated, notably type 2 and type 10 collagens, COMP and Sox9. The sequential combination of TGF-β1 and BMP-2 produced a similar profile with prominent expression of type 2 collagen and the alkaline phosphatase gene. Interestingly, in this in vitro condition, RUNX2 was not up-regulated, suggesting that the sequential combination of TGF-β1/BMP2 enhances the hypertrophic chondrogenic profile without turning towards the osteoblastic pathway. [ABSTRACT FROM AUTHOR]

Distal tibia fractures are complex injuries with a high complication rate. In this retrospective and multicentre study we attempted to detail complications and outcomes of this type of injury in order to determine predictive factors of poor results. Between 2002 and 2004, 104 patients were admitted for 105 distal tibia fractures. One hundred patients (101 fractures) were reviewed with an average follow-up of 19 months (range, 12-46). Internal fixation, external fixation, limited internal fixation (K-wires or screws), intramedullary nailing and conservative treatment were used. Outcome parameters included occurrence of complications, radiographic analysis, evaluation of the American Orthopaedic Foot and Ankle Society (AOFAS) ankle score and measures of the ankle range of motion. The average functional score was 76 points (range, 30-100 points), and complications occurred in 30 patients. Predictive factors of poor results were fracture severity, complications, malunion and the use of external fixation. We believe that external fixation must be reserved for trauma with severe skin injury, as a temporary solution in a two-staged protocol. For other cases, we recommend ORIF with early mobilisation. [ABSTRACT FROM AUTHOR]

Abstract: In this work, we designed replica particles based on poly (l-lysine) (PLL) polymers crosslinked via a homobifunctional linker to support coadsorption of a plasmid DNA and a peptide hormone for concurrent transfection and induction of a cellular function. PLL replica particles (PLLRP) were prepared by infiltrating polymer into mesoporous silica (MS) particles, crosslinking the adsorbed chains by using a homobifunctional crosslinker and finally removing the template particles. Moreover, we verified their cytotoxicity. Furthermore, based on this PLLRP gene delivery system, we simultaneously evaluated the melanin stimulation and gene expression in these cells by fluorescence microscopy. To further understand the bi-functionality, we labeled the SPT7pTL and PGA-α-MSH with YOYO-1 and Rhodamine, respectively, to follow its intracellular pathway by confocal microscopy. Our data suggests that the PLLRP is a promising vector for gene therapy and hormone stimulation. [Copyright &y& Elsevier]

This article reports the technique of percutaneous autologous bone marrow injection as a minimally invasive method alternative to open grafting techniques in the treatment of delayed unions and non-unions. Despite continuous advances in the treatment of long bone fractures, disturbances of healing processes remain a difficult challenge for orthopaedic surgeons. Percutaneous administration of substances with osteoinductive and osteogenic properties offers the advantage of decreased morbidity associated with the classic open grafting techniques. This makes it worth exploring before embarking on more extensive open surgery. The authors present the main technical stages of the percutaneous bone marrow grafting (bone marrow aspiration, concentration, intra-osseous re-injection and post-operative protocol) with a short literature review about this topic. [ABSTRACT FROM AUTHOR]

Osteoarthritis and rheumatoid arthritis are characterized by loss of proteoglycans (PGs) and their glycosaminoglycan (GAG) chains that are essential for cartilage function. Here, we investigated the role of glycosyltransferases (GTs) responsible for PC-GAG chain assembly during joint cartilage destruction and repair processes. At various times after antigen-induced arthritis (AIA) and papain-induced cartilage repair in rats, PG synthesis and deposition, expression of GTs, and GAG chain composition were analyzed. Our data showed that expression of the GT xylosyltransferase I (XT-I) gene initiating PG-GAG chain .synthesis was significantly reduced in AIA rat cartilage and was associated with a decrease in PG synthesis. Interestingly, interleukin-1β, the main proinflammatory cytokine incriminated in joint diseases, down-regulated the XT-I gene expression with a concomitant decrease in PG synthesis in rat cartilage explants ex vivo. However, cartilage from papain-injected rat knees showed upregulation of XT-I gene expression and increased PG synthesis at early stages of cartilage repair, a process associated with up-regulation of TGF-β1 gene expression and mediated by p38 mitogen-activated protein kinase activation. Consistently, silencing of XT-I expression by intraarticular injection of XT-I shRNA in rat knees prevented cartilage repair by decreasing PG synthesis and content. These findings show that GTs play a key role in the loss of PG-GAGs in joint diseases and identify novel targets for stimulating cartilage repair. [ABSTRACT FROM AUTHOR]

The article presents a study that aims to identify regulators of the cartilaginous phenotype based on differential expression in human conventional chondrogenic tumors. Result of the study shows that increased expression of the cartilage-specific matrix protein was specifically observed in enchondromas and conventional chondrosarcomas. It notes that aberrant expression and processing of matrilin-3 (MATN3) are hallmarks of conventional cartilaginous neoplasm.

We report a case of a 29-year-old woman suffering from chronic factitious disorder (FD) with torsion dystonia. For nearly five years, she traveled widely over the country, going from one hospital to another, taking serious medical risk in order to prolong her illness. After several admissions to Rehabilitation Units and multiple explorations, we find convincing evidence for factitious origin and the diagnosis of Munchausen syndrome was evoked. Such a clinical presentation is infrequent in Munchausen's syndrome. Indeed, most often the clinical picture is characterized by acute abdominal pain, fainting, hemoptysis, precordialgia, hematemesis or dermatological lesions. Physicians should be aware of this rare and potentially critical form of FD. Awareness in identifying these patients may lead to prevent unnecessary medical and/or surgical interventions. [ABSTRACT FROM AUTHOR]

The authors report a case of reversible ischemia of the foot in a 21-year-old male victim of a road traffic accident with a severe closed injury of the foot. His medical history was unremarkable. X-rays revealed multiple fractures of the foot without any lesion of the ankle. Physical examination of the dorsalis pedis and posterior tibial arteries showed no peripheral pulse. No blood flow was perceptible by Doppler assessment. The examination of the leg was unremarkable with normal temperature and coloration of the skin. A surgical approach of the posterior tibial artery was decided which revealed a severe vasospasm of the artery without rupture. The application in the wound of a warm serum permitted the progressive revascularization of the foot. Peripheral vasospasm is a condition classically observed with vasospastic drugs, in metabolic or vascular diseases or after cold exposure especially in the hand. Involvement of the foot is quite rare especially in trauma conditions. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) are found in synovial fluid (SF) and can easily be harvested during arthrocentesis or arthroscopy. However, SF-MSC characterization and chondrogenicity in collagen sponges have been poorly documented as well as their hypothetical in vivo chondroprotective properties with intra-articular injections during experimental osteoarthritis (OA). Methods: SF-MSCs were isolated from human SF aspirates in patients suffering from advanced OA undergoing total knee joint replacements. SF-MSCs at passage 2 (P2) were characterized by flow cytometry for epitope profiling. SF-MSCs at P2 were subsequently cultured in vitro to assess their multilineage potentials. To assess their chondrogenicity, SF-MSCs at P4 were seeded in collagen sponges for 4 weeks under various oxygen tensions and growth factors combinations to estimate their gene profile and matrix production. Also, SF-MSCs were injected into the joints in a nude rat anterior cruciate ligament transection (ACLT) to macroscopically and histologically assess their possible chondroprotective properties,. Results: We characterized the stemness (CD73+, CD90+, CD105+, CD34−, CD45−) and demonstrated the multilineage potency of SF-MSCs in vitro. Furthermore, the chondrogenic induction (TGF-ß1 ± BMP-2) of these SF-MSCs in collagen sponges demonstrated a good capacity of chondrogenic gene induction and extracellular matrix synthesis. Surprisingly, hypoxia did not enhance matrix synthesis, although it boosted chondrogenic gene expression (ACAN, SOX9, COL2A1). Besides, intra-articular injections of xenogenic SF-MSCs did exert neither chondroprotection nor inflammation in ACLT-induced OA in the rat knee. Conclusions: Advanced OA SF-MSCs seem better candidates for cell-based constructs conceived for cartilage defects rather than intra-articular injections for diffuse OA. [ABSTRACT FROM AUTHOR]