Summary Objective To examine the relationship between osteoarthritis (OA) and type 2 diabetes mellitus (DM). Methods OA cartilage from DM and non-DM patients undergoing knee replacement were ...stimulated by IL-1β for 24 h and release of interleukin-6 (IL-6) and prostaglandin E2 (PGE2 ) was measured. Primary cultured murine chondrocytes were stimulated for 24 and 72 h with or without IL-1β (5 ng/mL) under normal-glucose (5.5 mM) or high-glucose (25 mM) conditions. The expression and release of pro-inflammatory mediators (IL-6, cyclooxygenase 2 COX2/PGE2 ) were analyzed by quantitative RT-PCR and ELISA/EIA. Glucose uptake was assessed with (14 C)-2-deoxyglucose. Reactive oxygen species (ROS) and nitric oxide (NO) production were measured. To analyze the mechanism of IL-1β-induced inflammation, cells were pretreated or treated with inhibitors of glucose transport (cytochalasin B), the polyol pathway (epalrestat), mitochondrial oxidative stress (MitoTEMPO) or nitric oxide synthase ( l -NAME). Results With IL-1β stimulation, IL-6 and PGE2 release was greater in human DM than non-DM OA cartilage (2.7- and 3-fold, respectively) ( P < 0.05). In vitro , with IL-1β stimulation, IL-6 and COX2 mRNA expression, IL-6 and PGE2 release, and ROS and NO production were greater under high-than normal-glucose conditions in cultured chondrocytes. IL-1β–increased IL-6 release was reduced with cytochalasin B, epalrestat, l -NAME or MitoTEMPO treatment (−45%, −62%, −38% and −40%, respectively). Conclusion OA cartilages from DM patients showed increased responsiveness to IL-1β–induced inflammation. Accordingly, high glucose enhanced IL-1β–induced inflammation in cultured chondrocytes via oxidative stress and the polyol pathway. High glucose and diabetes may thus participate in the increased inflammation in OA.
Abstract Postoperative pain relief is one of the cornerstones of success of orthopaedic surgery. Development of new minimally-invasive surgical procedures, as well as improvements in pharmacological ...and local and regional techniques should result in optimal postoperative pain control for all patients. The analgesic strategy has to be efficient, with minimal side effects, and be easy to manage at home. Multimodal analgesia allows for a reduction of opiate use and thereby its side effects. Local and regional analgesia is a major component of this multimodal strategy, associated with optimal pain relief, even upon mobilization, and it has beneficial effects on postoperative recovery. Ultrasound guidance improves the success rate of distal nerve blocks and makes distal selective blockade possible, helping to preserve the limb's motility. Besides peripheral nerve blocks, local infiltration (incisional and/or intra-articular) is also important to consider. Duration of the nerve blockade is limited after a single injection. This must be taken into consideration to avoid the recurrence of pain when the patient returns home. Continuous perineural blocks using catheters are an option that can be easily managed at home with monitoring by home-care nurses. Extended-release liposomal bupivacaine and adjuvants such as dexamethasone could significantly enhance the duration of the sensory block, thereby reducing the indications for pain pumps. Non-pharmacological approaches, such as cryotherapy, hypnosis and acupuncture should not be ignored.
We hypothesize that chondrocytes from the deepest articular cartilage layer are pivotal in maintaining cartilage integrity and that the modification of their prehypertrophic phenotype to a ...hypertrophic phenotype will drive cartilage degradation in osteoarthritis.
Murine immature articular chondrocytes (iMACs) were successively cultured into three different culture media to induce a progressive hypertrophic differentiation. Chondrocyte were phenotypically characterized by whole-genome microarray analysis. The expression of IL-34 and its receptors PTPRZ1 and CSF1R in chondrocytes and in human osteoarthritis tissues was assessed by RT-qPCR, ELISA and immunohistochemistry. The expression of bone remodeling and angiogenesis factors and the cell response to IL-1β and IL-34 were investigated by RT-qPCR and ELISA.
Whole-genome microarray analysis showed that iMACs, prehypertrophic and hypertrophic chondrocytes each displayed a specific phenotype. IL-1β induced a stronger catabolic effect in prehypertrophic chondrocytes than in iMACs. Hypertrophic differentiation of prehypertrophic chondrocytes increased Bmp-2 (95%CI 0.78; 1.98), Bmp-4 (95%CI 0.89; 1.59), Cxcl12 (95%CI 2.19; 5.41), CCL2 (95%CI 3.59; 11.86), Mmp 3 (95%CI 10.29; 32.14) and Vegf mRNA expression (95%CI 0.20; 1.74). Microarray analysis identified IL-34, PTPRZ1 and CSFR1 as being strongly overexpressed in hypertrophic chondrocytes. IL-34 was released by human osteoarthritis cartilage; its receptors were expressed in human osteoarthritis tissues. IL-34 stimulated CCL2 and MMP13 in osteoblasts and hypertrophic chondrocytes but not in iMACs or prehypertrophic chondrocytes.
Our results identify prehypertrophic chondrocytes as being potentially pivotal in the control of cartilage and subchondral bone integrity. Their differentiation into hypertrophic chondrocytes initiates a remodeling program in which IL-34 may be involved.
Summary Objective Avocado–Soybean Unsaponifiables (ASU) represent one of the most commonly used drugs for symptomatic osteoarthritis (OA). The mechanisms of its activities are still poorly ...understood. We investigate here the effects of ASU on signaling pathways in mouse or human chondrocytes. Methods Mouse or human chondrocytes stimulated with interleukin-1β (IL1β, 10 ng/ml) and cartilage submitted to a compressive mechanical stress (MS) were studied in the presence or absence of ASU (10 μg/ml). Nuclear factor κB (NF-κB) activation was assessed by immunoblot, using an I-κBα antibody, nuclear translocation of NF-κB using p65 antibody, and extra-cellular signal-regulated kinase (ERK)1/2 activation using phospho and ERK1/2 antibodies. The binding of the p50/p65 complex on DNA was studied by electrophoretic mobility shift assay. Results ASU decrease matrix metalloproteinases-3 and -13 expressions and Prostaglandin E2 (PGE2 ) release in our model. The degradation of I-κBα is prevented in the presence of ASU as shown by the persistent expression of I-κBα protein in the cytosol when chondrocytes are stimulated by IL1β or MS. Nuclear translocation of the NF-κB complex is shown by the decrease of the p65 protein from the cytosol, whereas p65 appears in the nucleus under IL1β stimulation. This translocation is abolished in the presence of ASU. Moreover, bandshift experiments show an inhibition of the IL1β-induced binding of p50/p65 complexes to NF-κB responsive elements in response to ASU. Finally, among the different mitogen-activated protein kinases known to be induced by IL1β, ERK1/2 was the sole kinase inhibited by ASU. Conclusion These results demonstrate that ASU express a unique range of activities, which could counteract deleterious processes involved in OA, such as inflammation.
Purpose
Volar locking plates, used in distal radius fracture (DRF), present a risk of injuring extensor tendons with screws penetrating the dorsal cortex of the radius. Actually, even when aiming to ...use maximum-length unicortical locking screws, some still could be bicortical. We hypothesize the use of only short unicortical screws would allow a proper stabilization of the radial epiphysis without the risk of dorsal cortex penetration.
Materials and methods
A prospective monocentric non-randomized study was conducted. Patients with DRF (excepted for partial dorsal joint fractures) were treated in group A with short locking epiphyseal screws (16 mm for females, 18 mm for males) and in group B with full-length unicortical locking screws. Ultrasound was done 3 months postoperatively to evaluate the number and length of prominent dorsal screws. X-rays were performed after 6 weeks to assess stability according to volar tilt and radial inclination variations.
Results
There were 37 patients in group A and 39 in group B with 148 and 156 epiphyseal screws, respectively. In group A, there were 0% of dorsal penetrating screws against 6.5% (10 screws from 8 patients) in group B (
p
< 0.05). There was no significant difference for the stability between the groups: mean volar tilt variation ( − 0.6° vs. − 0.7°) and mean radial inclination variation ( − 0.4° vs. − 0.4°).
Conclusion
For a same stability with volar locking plates for DRF, short epiphyseal locking screws should be preferred to full-length unicortical screws in order to prevent extensor tendon injuries. Based on 75% of distal radial average anteroposterior width for each sex, screw lengths of 16 mm for females and 18 mm for males seem to be the length to use.
Level of Evidence 2
Prospective, Comparisons made, non-randomized.
In this study, we have evaluated the ability of human satellite cells isolated from subjects aged from 5 days to 86 years to proliferate in culture. Cells were cultivated until they became senescent. ...The number of cell divisions was calculated by counting the number of cells plated in culture compared to the number of cells removed following proliferation. Telomere length, which is known to decrease during each round of cell division, has been used to analyze the in vitro replicative capacity and in vivo replicative history of human satellite cells at isolation. The rate of telomere shortening in myonuclei of these muscle biopsies was also examined. Our results show that both proliferative capacity and telomere length of satellite cells decreases with age during the first two decades but that the myonuclei of human skeletal muscle are remarkably stable because telomere length in these myonuclei remains constant from birth to 86 years. The lack of shortening of mean terminal restriction fragments (TRF) in vivo confirms that skeletal muscle is a stable tissue with little nuclear turnover and therefore an ideal target for cell-mediated gene therapy. Moreover, our results show that it is important to consider donor age as a limiting factor to obtain an optimal number of cells.
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