Wijnen, André J. van

A cancer-promoting histone protein Mutations in the chromatin protein histone H3 are found in a number of pediatric cancers. The lysine-36–to–methionine (K36M) “oncohistone” mutation is seen in almost all chondroblastomas. Fang et al. show that the K36M mutant histones inhibit the normal methylation of this same residue in wild-type H3 histones. They do so by interfering with the enzymes that normally methylate this residue. The altered chromatin methylation patterns alter the expression of known cancer-related genes and impart cancer-related characteristics to the chondrocyte cells. Science , this issue p. 1344

Background: Enchondromas are benign cartilage tumors that can cause pathologic fractures involving the digits of the hand. The purpose of this study is to identify objective reproducible clinical criteria that are associated with fracture that can be used to guide clinical decision making. Methods: A total of 54 enchondroma cases involving the hand were retrospectively reviewed. Criteria examined included age, gender, the hand involved (left vs right), bone involved, the digit involved, and longitudinal percentage of the bone occupied by the lesion on anteroposterior (AP) radiographs. Results: There was a statistically significant difference between the fracture and nonfracture group in regard to age, the digit involved, bone involved, and the percentage of bone occupied by the lesion on AP radiographs. Conclusion: This investigation provides evidence that patient age, the affected finger, the affected bone, and the percentage of the bone occupied by the pathologic lesion on AP radiographs can be used to predict pathologic fracture risk for enchondromas.

ABSTRACTPreservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA‐seq) and real‐time reverse transcription quantitative polymerase chain reaction (RT‐qPCR) to assess genome‐wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM‐related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950–1959, 2016.

Aims Animal models have been developed that allow simulation of post-traumatic joint contracture. One such model involves contracture-forming surgery followed by surgical capsular release. This model allows testing of antifibrotic agents, such as rosiglitazone. Methods A total of 20 rabbits underwent contracture-forming surgery. Eight weeks later, the animals underwent a surgical capsular release. Ten animals received rosiglitazone (intramuscular initially, then orally). The animals were sacrificed following 16 weeks of free cage mobilisation. The joints were tested biomechanically, and the posterior capsule was assessed histologically and via genetic microarray analysis. Results There was no significant difference in post-traumatic contracture between the rosiglitazone and control groups (33° (standard deviation (sd) 11) vs 37° (sd14), respectively; p = 0.4). There was no difference in number or percentage of myofibroblasts. Importantly, there were ten genes and 17 pathways that were significantly modulated by rosiglitazone in the posterior capsule. Discussion Rosiglitazone significantly altered the genetic expression of the posterior capsular tissue in a rabbit model, with ten genes and 17 pathways demonstrating significant modulation. However, there was no significant effect on biomechanical or histological properties. Cite this article: M. P. Abdel. Effectiveness of rosiglitazone in reducing flexion contracture in a rabbit model of arthrofibrosis with surgical capsular release: A biomechanical, histological, and genetic analysis. Bone Joint Res 2016;5:11–17. doi: 10.1302/2046-3758.51.2000593

Purpose Several bioabsorbable and metal options are available for internal fixation of an unstable osteochondritis dissecans (OCD) lesion, but currently there are little data on outcomes with metal headless compression screws in the adult knee. The purpose of this study was to determine (1) the radiographic healing rates, (2) midterm clinical outcomes, and (3) comparison between healed and unhealed OCD fragments after use of headless metal compression screws for the treatment of unstable OCD lesions in the knees of skeletally mature patients. Methods Retrospective chart review for all skeletally mature patients who presented with unstable femoral condyle OCD lesions of the knee was conducted. All patients underwent open or arthroscopic reduction and internal fixation using headless metal compression screws. Preoperative and postoperative radiographs were reviewed with healing defined as radiographic evidence of union of the OCD progeny fragment with the condyle. Clinical outcome data were collected retrospectively using 3 validated outcome scores: International Knee Documentation Committee (IKDC), Knee Injury and Osteoarthritis Outcome Score (KOOS), and Marx. Results Twenty-two knees in 22 patients with a mean age of 21 years (range= 14-37 years) were followed for an average of 8.7 years (range = 2-22 years). Metal, headless, cannulated compression screws were used in all 22 cases. At a mean of 31 months postoperatively (range = 2-262), fragment union was observed in 18 knees (82%). The remaining 4 knees (18%) required loose fragment excision and hardware removal at a mean of 9 months (range = 2-16 months) postoperatively. Mean postoperative Marx score was 7 (range = 0-16), the mean postoperative IKDC score was 85 (range = 62-100), and mean KOOS scores included KOOS Pain (93; range = 69-100), KOOS Symptoms (86; range = 71-100), KOOS ADL (98; range = 90-100), KOOS Sports (82; range = 50-100), and KOOS QOL (76; range = 50-100). Conclusion Headless metal compression screws provide a satisfactory union rate for treatment of unstable OCD lesions of the femoral condyles in skeletally mature patients. Patients achieving union have good knee function, maintain satisfactory activity levels, and have superior knee outcomes compared with those that failed to heal after fixation at mid to long-term follow-up.

ABSTRACTLike any foreign object, orthopaedic implants are susceptible to infection when introduced into the human body. Without additional preventative measures, the absolute number of annual prosthetic joint infections will continue to rise, and may exceed the capacity of health care systems in the near future. Bacteria are difficult to eradicate from synovial joints due to their exceptionally diverse taxonomy, complex mechanistic attachment capabilities, and tendency to evolve antibiotic resistance. When a primary orthopaedic implant fails from prosthetic joint infection, surgeons are generally challenged by limited options for intervention. In this review, we highlight the etiology and taxonomic groupings of bacteria known to cause prosthetic joint infections, and examine their key mechanisms of attachment. We propose that antimicrobial strategies should focus on the most harmful bacteria taxa within the context of occurrence, taxonomic diversity, adhesion mechanisms, and implant design. Patient‐specific identification of organisms that cause prosthetic joint infections will permit assessment of their biological vulnerabilities. The latter can be targeted using a range of antimicrobial techniques that exploit different colonization mechanisms including implant surface attachment, biofilm formation, and/or hematogenous recruitment. We anticipate that customized strategies for each patient, joint, and prosthetic component will be most effective at reducing prosthetic joint infections, including those caused by antibiotic‐resistant and polymicrobial bacteria. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:177–186, 2016.

Renovascular hypertension (RVH) leads to left ventricular (LV) hypertrophy and diastolic dysfunction, associated with increased cardiovascular mortality. Intrarenal delivery of endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) improves kidney function in porcine RVH, and the potent anti-inflammatory properties of MSCs may serve to blunt inflammatory mediators in the cardiorenal axis. However, their relative efficacy in attenuating cardiac injury and dysfunction remains unknown. This study tested the hypothesis that the car-dioprotective effect of EPCs and MSCs delivered into the stenotic kidney in experimental RVH are comparable. Pigs ( n = 7 per group) were studied after 10 weeks of RVH or control untreated or treated with a single intrarenal infusion of autologous EPCs or MSCs 4 weeks earlier. Cardiac and renal function (fast CT) and stenotic kidney release of inflammatory mediators (ELISA) were assessed in vivo, and myocardial inflammation, remodeling, and fibrosis ex vivo. After 10 weeks of RVH, blood pressure was not altered in cell-treated groups, yet stenotic kidney glomerular filtration rate (GFR), blunted in RVH, improved in RVH + EPC, and normalized in RVH + MSCs. Stenotic kidney release of monocyte chemoattractant protein (MCP)-1 and its myocardial expression were elevated in RVH + EPC, but normalized only in RVH + MSC pigs. RVH-induced LV hypertrophy was normalized in both EPC- and MSC-treated pigs, while diastolic function (E/A ratio) was restored to normal levels exclusively in RVH + MSCs. RVH-induced myocardial fibrosis and collagen deposition decreased in RVH + EPCs but further decreased in RVH + MSC-treated pigs. Intrarenal delivery of EPCs or MSCs attenuates RVH-induced myocardial injury, yet MSCs restore diastolic function more effectively than EPCs, possibly by greater improvement in renal function or reduction of MCP-1 release from the stenotic kidney. These observations suggest a therapeutic potential for EPCs and MSCs in preserving the myocardium in chronic experimental RVH.