Patient with knee osteoarthritis demonstrates improved knee adduction moment after knee joint distraction: a case report.

In this article we report a case of a 53-year-old patient diagnosed with end-stage osteoarthritis (OA) of the knee. The patient underwent treatment with knee joint distraction (KJD) with the aim to postpone total knee arthroplasty and prevent potential revision surgery. To assess the effect of KJD, a 3D gait analysis was performed preoperative and one year postoperative. In this patient, preoperative 3D gait analysis revealed an increased knee adduction moment (KAM) compared to healthy levels. Postoperative the KAM decreased, approaching healthy levels, suggesting potential improvements in disease status or in gait. Consequently, further investigation into the effectiveness of Knee Joint Distraction (KJD) as a treatment option for relatively young patients with knee OA is warranted. Gait analysis has emerged as an effective tool for assessing treatment outcomes of innovative treatment such as KJD at the individual level.

Cartilage repair strategies in the knee according to Dutch Orthopedic Surgeons: a survey study.

BACKGROUND: This study surveyed Dutch orthopedic surgeons on the management of cartilage defects in the knee and the adherence to the recently updated Dutch knee cartilage repair consensus statement (DCS). METHODS: A web-based survey was sent to 192 Dutch knee specialists. RESULTS: The response rate was 60%. Microfracture, debridement and osteochondral autografts are performed by the majority, 93%, 70% and 27% of respondents, respectively. Complex techniques are used by < 7%. Microfracture is mainly considered in defects 1-2 cm2 (by > 80%) but also in 2-3 cm2 (by > 40%). Concomitant procedures, e.g., malalignment corrections, are performed by 89%. Twenty-one percent of surgeons treat patients aged 40-60 years. Microfracture, debridement and autologous chondrocyte implantation are not considered to be highly affected by age > 40 years by any of the respondents (0-3%). Moreover, for the middle-aged there is a large spread in treatments considered. In case of loose bodies, the majority (84%) only performs refixation in the presence of attached bone. CONCLUSION: Small cartilage defects in ideal patients may be well treated by general orthopedic surgeons. The matter becomes complicated in older patients, or in case of larger defects or malalignment. The current study reveals some knowledge gaps for these more complex patients. Referral to tertiary centers might be indicated, as is stated by the DCS, and this centralization should enhance knee joint preservation. Since the data from present study are subjective, registration of all separate cartilage repair cases should fuel objective analysis of clinical practice and adherence to the DCS in the future.

Direct comparison of non-osteoarthritic and osteoarthritic synovial fluid-induced intracellular chondrocyte signaling and phenotype changes.

OBJECTIVE: Since the joint microenvironment and tissue homeostasis are highly dependent on synovial fluid, we aimed to compare the essential chondrocyte signaling signatures of non-osteoarthritic vs end-stage osteoarthritic knee synovial fluid. Moreover, we determined the phenotypic consequence of the distinct signaling patterns on articular chondrocytes. METHODS: Protein profiling of synovial fluid was performed using antibody arrays. Chondrocyte signaling and phenotypic changes induced by non-osteoarthritic and osteoarthritic synovial fluid were analyzed using a phospho-kinase array, luciferase-based transcription factor activity assays, and RT-qPCR. The origin of osteoarthritic synovial fluid signaling was evaluated by comparing the signaling responses of conditioned media from cartilage, synovium, infrapatellar fat pad and meniscus. Osteoarthritic synovial fluid induced pathway-phenotype relationships were evaluated using pharmacological inhibitors. RESULTS: Compared to non-osteoarthritic synovial fluid, osteoarthritic synovial fluid was enriched in cytokines, chemokines and growth factors that provoked differential MAPK, AKT, NFκB and cell cycle signaling in chondrocytes. Functional pathway analysis confirmed increased activity of these signaling events upon osteoarthritic synovial fluid stimulation. Tissue secretomes of osteoarthritic cartilage, synovium, infrapatellar fat pad and meniscus activated several inflammatory signaling routes. Furthermore, the distinct pathway signatures of osteoarthritic synovial fluid led to accelerated chondrocyte dedifferentiation via MAPK/ERK signaling, increased chondrocyte fibrosis through MAPK/JNK and PI3K/AKT activation, an elevated inflammatory response mediated by cPKC/NFκB, production of extracellular matrix-degrading enzymes by MAPK/p38 and PI3K/AKT routes, and enabling of chondrocyte proliferation. CONCLUSION: This study provides the first mechanistic comparison between non-osteoarthritic and osteoarthritic synovial fluid, highlighting MAPKs, cPKC/NFκB and PI3K/AKT as crucial OA-associated intracellular signaling routes.

The first-generation anatomical medial meniscus prosthesis led to unsatisfactory results: a first-in-human study.

PURPOSE: The purpose of this first-in-human study was to evaluate the effect of a polycarbonate anatomical meniscus prosthesis system, including the surgical procedure, on knee pain and describe potential adverse events in patients with post-meniscectomy pain syndrome. METHODS: Eleven patients with post-meniscectomy pain syndrome and limited underlying cartilage damage were enrolled in the study. Five received a medial polycarbonate urethane meniscus prosthesis which was clicked onto 2 titanium screws fixated at the native horn attachments on the tibia. The KOOS score was planned to be collected at baseline and at 3, 6, 12 and 24 months following the intervention including radiographs at 6, 12 and 24 months. MRI scans were repeated after 12 and 24 months. RESULTS: The surgical technique to select an appropriately sized implant and correct positioning of the fixation screws and meniscus prosthesis onto the tibia was demonstrated to be feasible and reproducible. Inclusion stopped after 5 patients because of serious adverse device-related events. All patients reported knee joint stiffness and slight effusion in their knee at 6 months follow-up. In 3 patients the implant was removed because of implant failure and in 1 patient the implant was removed because of persistent pain and extension limitation. In none of the patients did the KOOS score improve in the first 6 months after surgery. However, in the patient who still has the implant in situ, PROMs started to improve 1 year after surgery and this improvement continued through 2 years of follow-up. The KOOS Pain, symptoms and ADL were close to the maximal 100 points. KOOS QoL and sport did improve but remained suboptimal. CONCLUSION: This first version of the meniscus prosthesis led to impaired knee function and failed in four out of five patients. The patients where the prosthesis was removed were salvable and the PROMs returned to pre-study levels. The results in the patient where the device is still in place are promising. LEVEL OF EVIDENCE: Level II.

Minced Autologous Chondral Fragments with Fibrin Glue as a Simple Promising One-Step Cartilage Repair Procedure: A Clinical and MRI Study at 12-Month Follow-Up.

OBJECTIVE: The aim of this study was to investigate early radiological and clinical outcome of autologous minced cartilage treatment as a single-step treatment option in patients with a chondral or osteochondral lesion (OCL) in the knee. DESIGN: Eighteen patients with an OCL in the knee were included. Cartilage from healthy-appearing loose bodies and/or the periphery of the defect were minced into small chips and sealed in the defect using fibrin glue. Preoperatively, and at 3 (n = 14) and 12 (n = 18) months follow-up, magnetic resonance imaging (MRI) was performed. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score was used to assess the cartilage repair tissue on MRI at 12 months. The International Knee Documentation Score, Knee Injury and Osteoarthritis Outcome Score, EuroQoL-5D, and Visual Analogue Scale pain were collected preoperatively and 12 months after surgery. RESULTS: Three months postoperative, MRI showed complete defect filling in 11 out of 14 patients. Mean MOCART 2.0 score at 12 months was 65.0 ± 18.9 with higher scores for lateral femoral chondral lesions compared to medial femoral chondral lesions (75.8 ± 14.3, 52.5 ± 15.8 respectively, P = 0.02). Clinical and statistical significant improvements were observed in the patient-reported outcome measures at 12 months postoperatively compared to preoperatively. CONCLUSION: Treatment of OCLs using the autologous minced cartilage procedure resulted in good cartilage repair measured by MOCART 2.0. Clinically relevant improvements were observed in the clinical scores. This study suggests autologous minced cartilage as a promising, single-step treatment for OCLs.

7-Tesla MRI Evaluation of the Knee, 25 Years after Cartilage Repair Surgery: The Influence of Intralesional Osteophytes on Biochemical Quality of Cartilage.

OBJECTIVE: To evaluate the morphological and biochemical quality of cartilage transplants and surrounding articular cartilage of patients 25 years after perichondrium transplantation (PT) and autologous chondrocyte transplantation (ACT) as measured by ultra-high-field 7-Tesla (7T) magnetic resonance imaging (MRI) and to present these findings next to clinical outcome. DESIGN: Seven PT patients and 5 ACT patients who underwent surgery on the femoral condyle between 1986 and 1996 were included. Patient-reported outcome measures (PROMs) were assessed by the clinical questionnaires: Knee injury and Osteoarthritis Outcome Score (KOOS), International Knee Documentation Committee (IKDC), and Visual Analogue Scale (VAS) for knee pain. The morphological (MOCART score) and biochemical quality (glycosaminoglycans [GAGs] content and collagen integrity) of cartilage transplants and surrounding articular cartilage were analyzed by 7T MRI. The results of the PT and ACT patients were compared. Finally, a detailed morphological analysis of the grafts alone was performed. RESULTS: No statistically significant difference was found for the PROMs and MOCART scores of PT and ACT patients. Evaluation of the graft alone showed poor repair tissue quality and high prevalence of intralesional osteophyte formation in both the PT and ACT patients. Penetration of the graft surface by the intralesional osteophyte was related to biochemically damaged opposing tibial cartilage; GAG content was significantly lower in patients with an osteophyte penetrating the graft surface. CONCLUSIONS: Both PT and ACT patients have a high incidence of intralesional osteophyte formation 25 years after surgery. The resulting biochemical damage to the opposing tibial cartilage might be dependent on osteophyte morphology.

Treatment of a coronal shear injury of the trochlea using a modified hedgehog-based technique through an anterior neurovascular interval approach: A case report.

INTRODUCTION AND IMPORTANCE: Surgical treatment for dislocated trochlear shear injuries is recommended due to its articular nature. However, the surgical exposure is often limited and large cartilaginous fragments with lack of subchondral bone stock makes a stable fixation technically challenging. Rapid swelling of the traumatized cartilage induces a size misfit between the cartilage of the fragment and the defect site. The use of a "modified hedgehog"-based technique might be a solution in these cases. However, this technique has only been described in chondral shear lesions of the knee. CASE PRESENTATION: A fifteen-year-old boy fell out of the still rings during gymnastics at school and suffered trauma to his elbow. A CT-scan of the right elbow showed a coronal shear injury of the trochlea with accompanied lateral condyle fracture of the humerus. The patient was treated throughout an anterior neurovascular approach with a modified hedgehog-based technique with triple fixation by creating an interlocking match of the cartilage, application of fibrin glue and additional screw fixation. CLINICAL DISCUSSION: The anterior neurovascular interval approach provides a clear exposure of the fracture site which is useful for anatomic reduction and triple fixation. The subsequent modified hedgehog-based technique has only been described once in children with shear-off chondral fragments of the knee, without additional screw fixation. Adding a screw fixation of the fragment creates some collateral damage to the cartilage and might not be necessary in future cases. CONCLUSION: The anterior neurovascular approach seems elegant and provides adequate exposure. Furthermore, a modified hedgehog-based technique delivers a stable triple fixation of the osteochondral fragment.

The Modified Hedgehog Technique to Repair Pure Chondral Shear-off Lesions in the Pediatric Knee.

OBJECTIVE: The paediatric knee is prone to pure chondral shear-off lesions due to the developing osteochondral unit. Refixation of the chondral fragment is commonly done using metalwork or absorbable biomaterials. Both fixation methods come with biomaterial-related drawbacks. Earlier work on chondral allografts for cartilage repair in adults has shown successful osteochondral integration when the chondral allograft is treated with multiple incisions and then glued to the subchondral bone using fibrin glue. This is commonly referred to as the "hedgehog technique." This study investigates the feasibility of a modification of the hedgehog technique in autologous cartilage to repair shear-off lesions in children. DESIGN: Three consecutive patients (aged 11, 12, and 14 years) with shear-off chondral fragments of 2, 5, and 8 cm2 were treated using this modified hedgehog technique. The calcified side of the chondral fragments were multiply incised and trimmed obliquely for an interlocking fit in the defect site. Fibrin glue and, if indicated sutures, were applied to fix the fragment to the defect. In 1 patient, an anterior cruciate ligament (ACL) repair was also performed. Patients were evaluated clinically and by magnetic resonance imaging (MRI) up to 12 months postoperatively. RESULTS: Twelve months after surgery, all patients reported no pain and showed complete return to sport and full range of motion. MRI showed no signs of fragment loosening. CONCLUSIONS: The modified hedgehog technique is a feasible treatment option to repair pure chondral shear-off lesions in the paediatric knee. This was the first time this technique was used in autografting.

Protein Intake Falls below 0.6 g•kg-1•d-1 in Healthy, Older Patients Admitted for Elective Hip or Knee Arthroplasty.

OBJECTIVE: Hospitalization is generally accompanied by changes in food intake. Patients typically receive hospital meals upon personal preference within the framework of the food administration services of the hospital. In the present study, we assessed food provision and actual food and snack consumption in older patients admitted for elective hip or knee arthroplasty. DESIGN: A prospective observational study. SETTING: Orthopedic nursing ward of the Maastricht University Medical Centre+. PARTICIPANTS: In the present study, n=101 patients (age: 67±10 y; hospital stay: 6.1±1.8 d) were monitored during hospitalization following elective hip or knee arthroplasty. MEASUREMENTS: Energy and protein provided by self-selected hospital meals and snacks, and actual energy and protein (amount, distribution, and source) consumed by patients was weighed and recorded throughout 1-6 days. RESULTS: Self-selected meals provided 6.5±1.5 MJ•d-1, with 16, 48, and 34 En% provided as protein, carbohydrate, and fat, respectively. Self-selected hospital meals provided 0.75±0.16 and 0.79±0.21 g•kg-1•d-1 protein in males and females, respectively. Actual protein consumption averaged merely 0.59±0.18 and 0.50±0.21 g•kg-1•d-1, respectively. Protein consumption at breakfast, lunch, and dinner averaged 16±8, 18±9, and 20±6 g per meal, respectively. CONCLUSIONS: Though self-selected hospital meals provide patients with ~0.8 g•kg-1•d-1 protein during short-term hospitalization, actual protein consumption falls well below 0.6 g•kg-1•d-1 with a large proportion (~32%) of the provided food being discarded. Alternative strategies are required to ensure maintenance of habitual protein intake in older patients admitted for elective orthopedic surgery.

Controlled release of celecoxib inhibits inflammation, bone cysts and osteophyte formation in a preclinical model of osteoarthritis.

Major hallmarks of osteoarthritis (OA) are cartilage degeneration, inflammation and osteophyte formation. COX-2 inhibitors counteract inflammation-related pain, but their prolonged oral use entails the risk for side effects. Local and prolonged administration in biocompatible and degradable drug delivery biomaterials could offer an efficient and safe treatment for the long-term management of OA symptoms. Therefore, we evaluated the disease-modifying effects and the optimal dose of polyesteramide microspheres delivering the COX-2 inhibitor celecoxib in a rat OA model. Four weeks after OA induction by anterior cruciate ligament transection and partial medial meniscectomy, 8-week-old female rats (n = 6/group) were injected intra-articular with celecoxib-loaded microspheres at three dosages (0.03, 0.23 or 0.39 mg). Unloaded microspheres served as control. During the 16-week follow-up, static weight bearing and plasma celecoxib concentrations were monitored. Post-mortem, micro-computed tomography and knee joint histology determined progression of synovitis, osteophyte formation, subchondral bone changes, and cartilage integrity. Systemic celecoxib levels were below the detection limit 6 days upon delivery. Systemic and local adverse effects were absent. Local delivery of celecoxib reduced the formation of osteophytes, subchondral sclerosis, bone cysts and calcified loose bodies, and reduced synovial inflammation, while cartilage histology was unaffected. Even though the effects on pain could not be evualated directly in the current model, our results suggest the application of celecoxib-loaded microspheres holds promise as novel, safe and effective treatment for inflammation and pain in OA.

Disease burden of knee osteoarthritis patients with a joint replacement compared to matched controls: a population-based analysis of a Dutch medical claims database.

OBJECTIVE: On a population level, the incidence of knee prostheses (KPs) has increased, but excess health care costs per patient, compared to matched controls without a KP, in the years surrounding these procedures and their determinants are largely unknown. We therefore aimed to provide estimates of age- and sex-specific incidence of KPs, revision KPs, and prosthesis complications in patients with knee osteoarthritis (OA) and to determine excess health care costs in the years surrounding surgery compared with matched controls. METHODS: All KPs in OA patients in the Achmea Health Database were identified as well as up to four controls. Incidence rates of KPs, revisions, and complications from 2006 to 2013 were determined. Annual health care cost and excess costs (over matched controls) preceding, during, and after surgery were calculated and their determinants were evaluated. RESULTS: The increased incidence of KPs, revisions, and complications was strongest in younger age categories and men. The average costs per patient were relatively stable between 2006 and 2012. KP patient's annual health care costs increased towards the year of surgery. After surgery, costs decreased, but remained higher as compared to costs prior to surgery. High post-surgery costs were mainly associated with subsequent revisions or additional KPs, but costs were also higher in females, lower age categories, and lower social economic status. CONCLUSION: These results underscore the increasing burden and medical need associated with end-stage OA, especially in younger age categories. Improvement of guidelines tailored to individual patient groups aimed at avoiding complications and revisions is required to counteract this increasing burden.

Patient-specific instrumentation in Oxford unicompartmental knee arthroplasty is reliable and accurate except for the tibial rotation.

PURPOSE: Patient-specific instrumentation (PSI) is a technique to plan and position the prosthesis components in unicompartmental knee arthroplasty (UKA) surgery. This study assesses whether the definitive component position in the frontal, sagittal and axial plane is according to the preoperative plan, based on the hypothesis that PSI is accurate. METHODS: Twenty-six patients who had PSI Oxford UKA surgery were included prospectively. The component position in vivo was determined with a postoperative CT-scan and compared with the planned component position using MRI-based digital 3D imaging. Adjustments to the preoperative plan and implanted component sizes during surgery were recorded. RESULTS: Intraoperatively, no femoral adjustments were performed; 12 tibial re-resections were necessary. The median absolute deviation from the plan in degrees (range) in the frontal, sagittal and axial plane was 1.8° (- 1.5°-6.5°), 2.0° (- 6.5°-8.0°) and 1.0° (- 1.5°-5.0°) for the femoral component, and 2.5° (- 1.0°-6.0°), 3.0° (- 1.0°-5.0°) and 5.0° (- 6.5°-12.5°) for the tibial component. The femoral component is positioned 0.5 (- 1°-2.5°) mm more lateral and 0.8 (- 1.0°-2.5°) mm more anterior. The tibial component is positioned 2.0 (- 5.0-0.0) mm more lateral and 1.3 (- 3.0-6.0) mm more distal. The femoral and tibial default plans were changed four times (15.4%) and nine times (34.6%), respectively, before approval by the surgeon. CONCLUSION: PSI in Oxford UKA surgery is reliable and accurately translates the preoperative plan into the in vivo situation, except for the tibial rotational position. The preoperative planning is a crucial step in avoiding re-resections that can cause angular deviations in prosthesis position, especially in tibial component rotational position. It is advised to avoid re-resections and to consider this while planning the PSI procedure. LEVEL OF EVIDENCE: Prospective comparative study Level II.

Comparison of fixed and mobile-bearing total knee arthroplasty in terms of patellofemoral pain and function: a prospective, randomised, controlled trial.

BACKGROUND: Despite growing evidence in the literature, there is still a lack of consensus regarding the use of the mobile-bearing (MB) design total knee arthroplasty (TKA). METHODS: In a prospective, comparative, randomised, single centre trial, 106 patients with end-stage osteoarthritis of the knee were randomised to either an MB or fixed-bearing (FB) group to receive posterior stabilised (PS)-TKA using a standard medial parapatellar approach and patellar resurfacing with follow-up (FU) for 5 years. The primary outcome was anterior knee pain (AKP) during the chair rise test and the stair climb test 5 years after surgery. The secondary outcome was the ability to rise from a chair and to climb stairs, range of motion (ROM), Knee Society Score (KSS), RAND-36 scores and radiological analysis of the patellar tilt. RESULTS: No statistically significant difference was found between the two groups at 5 years FU in terms of median AKP during the chair rise test and the stair climb test (p = 0.5 and p = 0.8, respectively). There was no significant difference in any of the other secondary outcome parameters between the groups at 5 years FU. CONCLUSION: A mobile-bearing TKA does not decrease AKP compared to fixed bearings. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02892838 . LEVEL OF EVIDENCE: II.

Cementless versus cemented Oxford unicompartmental knee arthroplasty: early results of a non-designer user group.

PURPOSE: Although fewer tibial radiolucent lines are observed in cementless Oxford unicompartmental knee arthroplasty (UKA) compared with cemented Oxford UKA, an independent comparative study on this topic is lacking. METHODS: In this multicentre retrospective study, a cohort of 60 consecutive cases of cementless Oxford UKA is compared with a cohort of 60 consecutive cases of cemented Oxford UKA. Radiolucent lines, survival, perioperative data and clinical results were compared. RESULTS: No complete tibial radiolucent lines were observed in either group. Seventeen per cent of partial tibial radiolucent lines were observed in the cementless group versus 21 % in the cemented group (n.s.). The percentage of tibial radiolucent zones was 4 versus 9 %, respectively (p = 0.036). Survival rates were 90 % at 34 months for the cementless group and 84 % at 54 months for the cemented group (n.s.). Mean operation time was 10 min shorter in the cementless group (p < 0.001), and clinical results were not significantly different. CONCLUSIONS: Although no significant differences in radiolucent lines were found between both groups, they appear to be more common in the cemented group. This confirms previous results from reports by prosthesis designers. The presence of radiolucent lines after cemented Oxford UKA does not correlate with clinical outcome or survival. LEVEL OF EVIDENCE: III.

Revision from unicompartmental to total knee replacement: the clinical outcome depends on reason for revision.

Although it has been suggested that the outcome after revision of a unicondylar knee replacement (UKR) to total knee replacement (TKR) is better when the mechanism of failure is understood, a comparative study on this subject has not been undertaken. A total of 30 patients (30 knees) who underwent revision of their unsatisfactory UKR to TKR were included in the study: 15 patients with unexplained pain comprised group A and 15 patients with a defined cause for pain formed group B. The Oxford knee score (OKS), visual analogue scale for pain (VAS) and patient satisfaction were assessed before revision and at one year after revision, and compared between the groups. The mean OKS improved from 19 (10 to 30) to 25 (11 to 41) in group A and from 23 (11 to 45) to 38 (20 to 48) in group B. The mean VAS improved from 7.7 (5 to 10) to 5.4 (1 to 8) in group A and from 7.4 (2 to 9) to 1.7 (0 to 8) in group B. There was a statistically significant difference between the mean improvements in each group for both OKS (p = 0.022) and VAS (p = 0.002). Subgroup analysis in group A, performed in order to define a patient factor that predicts outcome of revision surgery in patients with unexplained pain, showed no pre-operative differences between both subgroups. These results may be used to inform patients about what to expect from revision surgery, highlighting that revision of UKR to TKR for unexplained pain generally results in a less favourable outcome than revision for a known cause of pain.

Hypertrophic differentiation during chondrogenic differentiation of progenitor cells is stimulated by BMP-2 but suppressed by BMP-7.

OBJECTIVE: Bone morphogenic protein (BMP)-2 and BMP-7 are clinically approved and their recombinant proteins are used for bone tissue regenerative purposes and widely evaluated for cartilage regeneration. Previous comparison of the in vitro chondrogenic characteristics of BMP-2 vs BMP-7 did not address hypertrophic differentiation and characterizing their chondrogenic properties with a focus in on chondrocyte hypertrophy was topic of investigation in this study. DESIGN: Equimolar concentrations of BMP-2 or BMP-7 were added to chondrogenic differentiating ATDC5, human bone marrow stem cells or rabbit periosteal explants. Expression of Col2a1, Sox9, Acan, Col10a1, Runx2, ALP, Mmp13, Mef2c and Bapx1/Nkx3.2 was determined by reverse transcription-quantitative PCR (RT-qPCR) and immunoblotting. Glycosaminoglycan content, cell proliferation capacity and ALP activity were analysed by colourimetric analyses. Expression of Bapx1/Nkx3.2 and Sox9 was targeted by transfection of target specific siRNA duplexes. RESULTS: BMP-2 dose-dependently increased chondrocyte hypertrophy during chondrogenic differentiation of progenitor cells, whereas BMP-7 acted hypertrophy-suppressive and chondro-promotive. Both BMPs did not influence cell proliferation, but they did increase total glycosaminoglycan content. In a candidate approach Bapx1/Nkx3.2 was found to be involved in the BMP-7 mediated suppression of chondrocyte hypertrophy in ATDC5 cells. CONCLUSIONS: BMP-2 and BMP-7 display opposing actions on the chondrogenic outcome of differentiating progenitor cells: BMP-2 acts a specific inducer of chondrocyte hypertrophy, while BMP-7 appears to increase or maintain chondrogenic potential and prevent chondrocyte hypertrophy. Our results pave the way for an application-dependent differential use of BMP-2 or BMP-7.

Inhibition of cyclooxygenase-2 impacts chondrocyte hypertrophic differentiation during endochondral ossification.

Skeletogenesis and bone fracture healing involve endochondral ossification, a process during which cartilaginous primordia are gradually replaced by bone tissue. In line with a role for cyclooxygenase-2 (COX-2) in the endochondral ossification process, non-steroidal anti-inflammatory drugs (NSAIDs) were reported to negatively affect bone fracture healing due to impaired osteogenesis. However, a role for COX-2 activity in the chondrogenic phase of endochondral ossification has not been addressed before. We show that COX-2 activity fulfils an important regulatory function in chondrocyte hypertrophic differentiation. Our data reveal essential cross-talk between COX-2 and bone morphogenic protein-2 (BMP-2) during chondrocyte hypertrophic differentiation. BMP-2 mediated chondrocyte hypertrophy is associated with increased COX-2 expression and pharmacological inhibition of COX-2 activity by NSAIDs (e.g., Celecoxib) decreases hypertrophic differentiation in various chondrogenic models in vitro and in vivo, while leaving early chondrogenic development unaltered. Our findings demonstrate that COX-2 activity is a novel factor partaking in chondrocyte hypertrophy in the context of endochondral ossification and these observations provide a novel etiological perspective on the adverse effects of NSAIDs on bone fracture healing and have important implications for the use of NSAIDs during endochondral skeletal development.

Degradation of mesh coatings and intraperitoneal adhesion formation in an experimental model.

BACKGROUND: In laparoscopic ventral hernia repair a mesh is placed in direct contact with the viscera, often leading to substantial adhesions. In this experimental study the ability of different coated and uncoated meshes to attenuate adhesion formation was examined. METHODS: Six commercially available meshes were placed intraperitoneally against a closed peritoneum in rats: Prolene (polypropylene), Timesh and Ultrapro (polypropylene composites with titanium and polyglecaprone respectively), Proceed and Parietex Composite (polypropylene and polyester meshes coated with a layer of cellulose and collagen respectively) and C-Qur (polypropylene mesh coated with a layer of omega-3 fatty acids). Adhesions and incorporation were evaluated macroscopically and microscopically after 7 and 30 days. RESULTS: Parietex Composite and C-Qur significantly reduced adhesion formation at 7 days' follow-up compared with all other meshes. By 30 days, this effect had diminished as a significant increase in adhesions together with phagocytosis of the coating was seen for all meshes with layered coatings (Proceed, Parietex Composite and C-Qur. Incorporation was insufficient for all meshes. CONCLUSION: The absorbable layers of Parietex Composite and C-Qur reduce adhesion formation to intraperitoneal mesh in the short term, but the effect diminishes and phagocytosis of absorbable coatings may contribute to adhesion formation.