Objective. Mechanical signals are key determinants in tissue morphogenesis, maintenance, and restoration strategies in regenerative medicine, although molecular mechanisms of mechanotransduction remain to be elucidated. This study was undertaken to investigate the mechanotransduction process of expression of superficial zone protein (SZP), a critical joint lubricant.Methods. Regional expression of SZP was first quantified in cartilage obtained from the femoral condyles of immature bovines, using immunoblotting, and visualized by immunohistochemistry. Contact pressure mapping in whole joints was accomplished using pressure-sensitive film and a load application system for joint testing. Friction measurements on cartilage plugs were acquired under boundary lubrication conditions using a pin-on-disk tribometer modified for reciprocating sliding. Direct mechanical stimulation by shear loading of articular cartilage explants was performed with and without inhibition of transforming growth factor  (TGF) signaling, and SZP content in media was quantified by enzyme-linked immunosorbent assay.Results. An unexpected pattern of SZP localization in knee cartilage was initially identified, with anterior regions exhibiting high levels of SZP expression. Regional SZP patterns were regulated by mechanical signals and correlated with tribological behavior. Direct relationships were demonstrated between high levels of SZP expression, maximum contact pressures, and low friction coefficients. Levels of SZP expression and accumulation were increased by applying shear stress, depending on location within the knee, and were decreased to control levels with the use of a specific inhibitor of TGF receptor type I kinase and subsequent phospho-Smad2/3 activity.Conclusion. These findings indicate a new role for TGF signaling in the mechanism of cellular mechanotransduction that is especially significant for joint lubrication.Osteoarthritis (OA) is the most common form of arthritis, affecting 12.1% of US adults (1). Treatment of OA is a critical unmet need in biotechnology and medicine for the regeneration of damaged joints and articular cartilage in the elderly. During locomotion, animal joints allow for normal function by minimizing friction and wear (2,3). Superficial zone protein (SZP), a glycoprotein secreted by chondrocytes in the superficial layer of articular cartilage (4,5), is thought to be a key surface molecule or lubricant involved in boundary lubrication. SZP is also known as lubricin (6), megakaryocyte-stimulating factor precursor (7), and PRG4 (5). In addition to its function as a boundary lubricant, SZP inhibits synovial cell overgrowth (7). Down-regulation of SZP has been associated with the pathogenesis of OA (8). Dr. Schmid has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from the NIH and Auxilium. He holds a patent for anti-superficial zone protein monoclonal antibody and receives royalties for anti-collagen X monoclonal antibody.
The purpose of this study was to investigate the role of bone morphogenetic proteins (BMPs), such as BMP-7, growth factors, and cytokines, in the accumulation of superficial zone protein (SZP) in bovine articular cartilage. Calf superficial articular cartilage discs and chondrocytes were obtained for explant and monolayer culture systems, respectively. Dose-and time-dependent actions of BMP-7 on SZP accumulation were investigated in both explant and monolayer culture systems. In addition, actions of various morphogens and growth factors [BMP-2, BMP-4, fibroblast growth factor 2 (FGF-2), insulin-like growth factor 1 (IGF-1), platelet-derived growth factor (PDGF), and transforming growth factor b (TGF-b1)], and cytokines [interleukin (IL)-1a, IL-1b, and tumor necrosis factor (TNF-a)] alone, and in combination with BMP-7, on SZP accumulation were investigated in monolayer culture systems. SZP accumulation was quantified in both the cartilage and the medium using SDS-PAGE and subsequent immunoblotting. In both explant and monolayer cultures, BMP-7 increased SZP accumulation in a dose-and time-dependent fashion (p < 0.05). Furthermore, SZP accumulation was significantly increased in monolayer cultures by FGF-2, IGF-1, PDGF, and TGF-b1 (p < 0.05). Both IL-1a and TNF-a significantly reduced SZP accumulation (p < 0.05). The inhibition of SZP accumulation by TNF-a was partially alleviated by concurrent treatment with BMP-7. The results of this investigation provide novel insights into the role of morphogens, especially BMP-7, growth factors, and cytokines in the accumulation of SZP in articular cartilage. This information has clinical implications because stimulation of SZP may ameliorate the pathology of joint function in arthritis. Furthermore, tissue engineering approaches to articular cartilage may depend on the optimal synthesis and assembly of SZP in the superficial zone to ensure functional tissue architecture. ß
Our data reveal that the PFLP with the "kickstand" screw provides more axial stiffness, less torsional stiffness, and equivalent irreversible deformation to cyclic axial loading when compared with the blade plate.
Correct positioning of the LISS plate for fixation of distal femur fractures results in improved mechanical stability as reflected by an increased stiffness in axial loading and decreased plastic deformation at the bone-screw interface.
Although the Iso-C 3D imaging system was superior in delineating the joint surfaces, the image quality, and the overall clinical applicability, the study revealed that both devices provided 3D images with sufficient quality to the surgeon to assess clinically relevant questions, including the quality of fracture reduction and implant positioning. On the other hand, the Ziehm Vario 3D is capable of doing scans of the shoulder area, which could not be taken with the Siemens Iso-C 3D because of the isocentric design.
Overall, our results indicated that the Weil metatarsal neck osteotomy is effective at offloading the second metatarsal head at neutral and heel rise positions.
Introduction: The insertion site for an antegrade femoral intramedullary nail in the treatment of a femoral shaft fracture has traditionally been performed using a free-hand technique. An inappropriate starting point can result in suboptimal nail insertion leading to malreduction, or iatrogenic fracture. Furthermore, repeated attempts to establishthe optimal starting point cancause additional soft tissue trauma and radiation exposure. In the following study we compared a robot-guided technique with the standard free-hand technique for establishing the entry point of an antegrade femoral nail. We hypothesized that the robot-guided technique is more reliable and efficient.Methods: A custom-made drill-guide was mounted onto the arm of an industrial robot. Two orthogonal fluoroscopic images were acquired from the proximal femur of five cadaveric human specimens. Images were processed with a specialsoftwarein order to create an enhanced contour-recognition map from which the bone axes were automatically calculated. The drilling trajectory was computed along the extension of the bone-axis. The robot then moved the drill-guide on this trajectory toward the entry point. The drilling was then performed by the surgeon. In the control group, five cadaveric human femora were utilized to manually establish the starting pointusing the free-hand technique.Results: 100% of the intramedullary cavities were successfully accessed with both the robot-guided and the manual techniques. In the manual technique repositioning of the drill was necessary in three out of five cases. The mean number of acquired fluoroscopic images was significantly reduced from 11.6 (manual) to 4 (robot-guided).Conclusion: Robot-assisted drilling ofthe entry-point in antegrade femoral nailingis more reliable and requires fewer radiographic images than the free hand technique. Yet, based on economical and logistical considerations, its application will probably only be accepted when a concomitant application for fracture reduction is available.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.