Dupuytren's contracture-associated SNPs increase SFRP4 expression in non-immune cells including fibroblasts to enhance inflammation development.

Dupuytren's contracture (DC) is an inflammatory fibrosis characterized by fibroproliferative disorders of the palmar aponeurosis, for which there is no effective treatment. Although several genome-wide association studies have identified risk alleles associated with DC, the functional linkage between these alleles and the pathogenesis remains elusive. We here focused on two single nucleotide polymorphisms (SNPs) associated with DC, rs16879765 and rs17171229, in secreted frizzled related protein 4 (SFRP4). We investigated the association of SRFP4 with the IL-6 amplifier, which amplifies the production of IL-6, growth factors and chemokines in non-immune cells and aggravates inflammatory diseases via NF-κB enhancement. Knockdown of SFRP4 suppressed activation of the IL-6 amplifier in vitro and in vivo, whereas the overexpression of SFRP4 induced the activation of NF-κB-mediated transcription activity. Mechanistically, SFRP4 induced NF-κB activation by directly binding to molecules of the ubiquitination SFC complex, such as IkBα and ßTrCP, followed by IkBα degradation. Furthermore, SFRP4 expression was significantly increased in fibroblasts derived from DC patients bearing the risk alleles. Consistently, fibroblasts with the risk alleles enhanced activation of the IL-6 amplifier. These findings indicate that the IL-6 amplifier is involved in the pathogenesis of DC, particularly in patients harboring the SFRP4 risk alleles. Therefore, SFRP4 is a potential therapeutic target for various inflammatory diseases and disorders, including DC.

Trigger wrist caused by avascular necrosis of the capitate: a case report.

BACKGROUND: Trigger wrist is a rare condition first described by Marti in 1960, and various causes have been reported. The condition mostly occurs with finger flexion and extension, and rarely with flexion and extension of the wrist itself. Avascular necrosis of the capitate is also a rare condition, first described by Jönsson in 1942. While some reports of this condition have been published, little is known about its etiology. Therefore, no established treatment exists. We report a case of trigger wrist caused by avascular necrosis of the capitate. CASE PRESENTATION: A 16-year-old right-handed male who was a high school handball player was referred to our department from a nearby hospital 5 months after the onset of pain in the dorsal aspect of the right wrist, with an unknown cause. At the previous hospital, imaging findings led to a diagnosis of avascular necrosis of the capitate, and conservative treatment with a wrist brace did not improve the pain. At the initial visit to our department, the patient was noted to have a painful trigger wrist that was brought on by wrist flexion and extension. Preoperative imaging findings led to a diagnosis of trigger wrist caused by capitolunate instability secondary to avascular necrosis of the capitate. We performed a partial excision of the proximal capitate with tendon ball interposition. Two years after surgery, the patient's clinical outcome was favorable, with no recurrence of wrist pain or triggering. CONCLUSIONS: Both trigger wrist and avascular necrosis of the capitate are rare disorders. When a patient presents with painful triggering at the wrist, surgeons must bear in mind that avascular necrosis of the capitate may result in this phenomenon. We recommend partial excision of the proximal capitate with tendon ball interposition for the treatment of this lesion.

Implications of navigation system use for glenoid component placement in reverse shoulder arthroplasty.

Recently, three-dimensional (3D) planning, patient-specific instruments, and navigation system have been developed to improve the accuracy of baseplate placement in reverse shoulder arthroplasty (RSA). The purpose of this study was to evaluate baseplate placement using the navigation system. Sixty-four shoulders in 63 patients who underwent RSA for rotator cuff tear arthropathy or irreparable rotator cuff tears were enrolled. Conventional RSA was performed in 31 shoulders and navigated RSA using pre-operative planning software was performed in 33 shoulders. The use of augmented baseplates, the version and inclination of the baseplate, and screw length were compared between conventional RSA and navigated RSA. Augmented baseplates were used more frequently in navigated RSA than in conventional RSA (20 vs 9 shoulders, p = 0.014). Baseplate alignment was 1.0° (SD 5.1) of retroversion and 2.4° (SD 6.8) of superior inclination in conventional RSA and 0.2° (SD 1.9) of anteversion and 0.3° (SD 1.7) of superior inclination in navigated RSA. Compared with conventional RSA, precision of baseplate version and inclination were higher in navigated RSA (both p < 0.001). Superior, inferior, and posteroinferior screws were significantly longer in navigated RSA than in conventional RSA (p = 0.021, 0.001 and < 0.001, respectively). Precision of superior and inferior screw lengths was significantly higher in navigated RSA than in conventional RSA (both p = 0.001). Our results suggest that adoption of pre-operative planning software increased augmented baseplate use to minimize the glenoid reaming. The navigation system allows placement of the baseplate accurately, according to the pre-operative plan. Furthermore, the navigation system enables monitoring of screw length and direction in real time.

Determination of optimal concentration of vitamin E in polyethylene liners for producing minimal biological response to prosthetic wear debris.

The introduction of vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) for use in prosthetic components of hip implants has resulted in the production of implants that have excellent mechanical properties and substantially less adverse cellular responses. Given the importance of a biological response to wear in the survival of a prosthesis, we generated wear debris from UHMWPE that had been prepared with different concentrations of vitamin E of 0.1, 0.3, 0.5, and 1% and evaluated their biological reaction in vitro and in vivo. All types of VE-UHMWPE debris promoted a significantly lower expression of Tnf-α in murine peritoneal macrophages than that induced by conventional UHMWPE debris. However, levels of Tnf-α were not significantly different among the macrophages that were stimulated with VE-UHMWPE wear at the concentrations tested. The ability of wear debris to induce inflammatory osteolysis was assessed in a mouse calvarial osteolysis model. The expressions of Tnf-α, Il-6, and Rankl in granulomatous tissue formed around the wear debris were significantly reduced in mice that had been implanted with 0.3%VE-UHMWPE debris as compared to the corresponding values for mice that had been implanted with UHMWPE debris. Consistent with this finding, 0.3%VE-UHMWPE debris showed the lowest osteolytic activity, as evidenced by the reduced bone resorption area, the degree of infiltration of inflammatory cells and the TRAP staining area. Our results suggested that a 0.3% vitamin E concentration is the most appropriate concentration for use in prosthetic components with a reduced adverse cellular response for prolonging the life-span of the implant.

Blockade of XCL1/Lymphotactin Ameliorates Severity of Periprosthetic Osteolysis Triggered by Polyethylene-Particles.

Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.

Evaluation of the quality of Chinese and Vietnamese cassia using LC-MS and multivariate analysis.

In the present study, the chemical composition of water extracts of Chinese and Vietnamese cassia (Cinnamomum cassia) were compared using multivariate analysis of LC-MS data. By principal component analysis of the LC-MS data, 6 compounds, cinnzeylanine (1), cinnzeylanol (2), anhydrocinnzeylanol (3), cinncasinol A (4), epicatechin (5) and procyanidin B2 (6), were identified as the marker compounds to characterize Chinese and Vietnamese cassia. It was clarified that Chinese cassia contains relatively larger amounts of epicatechin and procyanidin B2. On the other hand, Vietnamese cassia is characterized by a relatively larger amount of diterpenes. As catechin derivatives and diterpenes have different types of activity, it is important to choose the cassia that best suits the product for which it is to be used, whether in food or in herbal medicine.

Qualitative and quantitative analysis of Swertia herbs by high performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS).

We evaluated the composition of Swertia herbs using high performance liquid chromatography-diode array detector-mass spectrometry (HPLC-DAD-MS). Eleven peaks of 6 species were unequivocally identified by comparing their retention times, UV spectra, on-line electrospray ionization mass (ESI-MS) spectra, and collision-induced dissociation mass spectrometry/mass spectrometry (CID-MS/MS) data with those of authentic compounds. We adopted wavelengths of 254 nm, 340 nm and 230 nm to simultaneously determine these 11 compounds. By comparing the overall DAD and total ion current (TIC) profiles of various samples, the 6 species were differentiated in terms of the occurrence and/or relative concentrations of the eleven compounds. Our novel validated HPLC-DAD-MS method not only facilitates quality control and identification of Swertia herbs, but is also applicable to systematic investigations of the distribution of secoiridoids, flavonoids, and xanthones in the genus Swertia.