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1.  Hypoxia and vitamin D differently contribute to leptin and dickkopf-related protein 2 production in human osteoarthritic subchondral bone osteoblasts 
Introduction
Bone remodelling and increased subchondral densification are important in osteoarthritis (OA). Modifications of bone vascularization parameters, which lead to ischemic episodes associated with hypoxic conditions, have been suspected in OA. Among several factors potentially involved, leptin and dickkopf-related protein 2 (DKK2) are good candidates because they are upregulated in OA osteoblasts (Obs). Therefore, in the present study, we investigated the hypothesis that hypoxia may drive the expression of leptin and DKK2 in OA Obs.
Methods
Obs from the sclerotic portion of OA tibial plateaus were cultured under either 20% or 2% oxygen tension in the presence or not of 50 nM 1,25-dihydroxyvitamin D3 (VitD3). The expression of leptin, osteocalcin, DKK2, hypoxia-inducible factor 1α (Hif-1α) and Hif-2α was measured by real-time polymerase chain reaction and leptin production was measured by enzyme-linked immunosorbent assay (ELISA). The expression of Hif-1α, Hif-2α, leptin and DKK2 was reduced using silencing RNAs (siRNAs). The signalling pathway of hypoxia-induced leptin was investigated by Western blot analysis and with mitogen-activated protein kinase (MAPK) inhibitors.
Results
The expression of leptin and DKK2 in Obs was stimulated 7-fold and 1.8-fold, respectively (P <0.05) under hypoxia. Interestingly, whereas VitD3 stimulated leptin and DKK2 expression 2- and 4.2-fold, respectively, under normoxia, it stimulated their expression by 28- and 6.2-fold, respectively, under hypoxia (P <0.05). The hypoxia-induced leptin production was confirmed by ELISA, particularly in the presence of VitD3 (P <0.02). Compared to Obs incubated in the presence of scramble siRNAs, siHif-2α inhibited VitD3-stimulated leptin mRNA and protein levels by 70% (P =0.004) and 60% (P <0.02), respectively, whereas it failed to significantly alter the expression of DKK2. siHif-1α has no effect on these genes. Immunoblot analysis showed that VitD3 greatly stabilized Hif-2α under hypoxic conditions. The increase in leptin expression under hypoxia was also regulated, by p38 MAPK (P <0.03) and phosphoinositide 3-kinase (P <0.05). We found that the expression of leptin and DKK2 were not related to each other under hypoxia.
Conclusions
Hypoxic conditions via Hif-2 regulation trigger Obs to produce leptin, particularly under VitD3 stimulation, whereas DKK2 is regulated mainly by VitD3 rather than hypoxia.
doi:10.1186/s13075-014-0459-3
PMCID: PMC4302570  PMID: 25312721
2.  Antegrade nailing evolution for proximal humeral fractures, the Telegraph IV®: a study of 67 patients 
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.
doi:10.1007/s00590-014-1493-1
PMCID: PMC4300429  PMID: 24947347
Proximal humeral fractures; Antegrade nailing; Locking screws
3.  Xylosyltransferase-I Regulates Glycosaminoglycan Synthesis during the Pathogenic Process of Human Osteoarthritis 
PLoS ONE  2012;7(3):e34020.
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 forced-expression 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-1β and up-regulated by TGF-β1 indicates that these cytokines may play a role in regulating GAG content in human OA. Noteworthy, expression of IL-1β receptor (IL-1R1) was down-regulated whereas that of TGF-β1 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.
doi:10.1371/journal.pone.0034020
PMCID: PMC3316535  PMID: 22479506
4.  Distal tibia fractures: management and complications of 101 cases 
International Orthopaedics  2009;34(4):583-588.
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.
doi:10.1007/s00264-009-0832-z
PMCID: PMC2903136  PMID: 19554328
5.  Obesity affects the chondrocyte responsiveness to leptin in patients with osteoarthritis 
Arthritis Research & Therapy  2010;12(3):R112.
Introduction
Increasing evidence support the regulatory role of leptin in osteoarthritis (OA). As high circulating concentrations of leptin disrupt the physiological function of the adipokine in obese individuals, the current study has been undertaken to determine whether the elevated levels of leptin found in the joint from obese OA patients also induce changes in the chondrocyte response to leptin.
Methods
Chondrocytes isolated from OA patients with various body mass index (BMI) were treated with 20, 100 or 500 ng/ml of leptin. The expression of cartilage-specific components (aggrecan, type 2 collagen), as well as regulatory (IGF-1, TGFβ, MMP-13, TIMP 2) or inflammatory (COX-2, iNOS, IL-1) factors was investigated by real-time PCR to evaluate chondrocyte responsiveness to leptin. Furthermore, the effect of body mass index (BMI) on leptin signalling pathways was analyzed with an enzyme-linked immunosorbent assay for STATs activation.
Results
Leptin at 20 ng/ml was unable to modulate gene expression in chondrocytes, except for MMP-13 in obese OA patients. Higher leptin levels induced the expression of IGF-1, type 2 collagen, TIMP-2 and MMP-13. However, the activity of the adipokine was shown to be critically dependent on both the concentration and the BMI of the patients with a negative association between the activation of regulated genes and BMI for 100 ng/ml of adipokine, but a positive association between chondrocyte responsiveness and BMI for the highest leptin dose. In addition, the gene encoding MMP-13 was identified as a target of leptin for chondrocytes originated from obese patients while mRNA level of TIMP-2 was increased in leptin-treated chondrocytes collected from normal or overweight patients. The adipokine at 500 ng/ml triggered signal transduction through a STAT-dependent pathway while 100 ng/ml of leptin failed to activate STAT 3 but induced STAT 1α phosphorylation in chondrocytes obtained from obese patients.
Conclusions
The current study clearly showed that characteristics of OA patients and more expecially obesity may affect the responsiveness of cultured chondrocytes to leptin. In addition, the BMI-dependent effect of leptin for the expression of TIMP-2 and MMP-13 may explain why obesity is associated with an increased risk for OA.
doi:10.1186/ar3048
PMCID: PMC2911905  PMID: 20534145
6.  Satisfaction with care after total hip or knee replacement predicts self-perceived health status after surgery 
Background
Inpatient satisfaction with care is a standard indicator of the quality of care delivered during hospitalization. Total hip and knee replacement (THR/TKR) for osteoarthritis (OA) are among the most successful orthopaedic interventions having a positive impact on health-related quality of life (HRQoL). The aim was to evaluate the effect of satisfaction shortly after hospital discharge on 1-month, 6-month and 1-year Medical Outcomes Study 36-item Short Form (SF-36) scores for OA patients after THR and TKR, controlling for patient characteristics, clinical presentation and preoperative SF-36 scores.
Methods
A multicenter prospective cohort study recruited 231 patients with OA scheduled to receive THR or TKR. Satisfaction was assessed by the Patients Judgment of Hospital Quality (PJHQ) questionnaire and HRQoL by the SF-36 questionnaire. Linear models for repeated measures assessed the relation between satisfaction (scores were dichotomized) and postoperative SF-36 scores.
Results
Of 231 participants, 189 were followed up 12 months after discharge (mean age 69 SD = 8; 42.6% male). The mean length of hospital stay was 13.5 (SD = 4) days. After adjustment for preoperative SF-36 scores, sociodemographic and clinical patient characteristics, satisfied patients (PJHQ score > 70) had higher SF-36 scores 1 year after surgery than did less-satisfied patients. Admission, medical care, and nursing and daily care scores mainly predicted bodily pain, mental health, social functioning, vitality and general health scores of the SF-36.
Conclusion
Besides being a quality-of-care indicator, immediate postoperative patient satisfaction with care may bring a new insight into clinical practice, as a predictor of self-perceived health status after surgery.
doi:10.1186/1471-2474-10-150
PMCID: PMC2795735  PMID: 19958520

Results 1-6 (6)