Journal of Orthopaedic Research
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Anti‐inflammatory effects of continuous passive motion on meniscal fibrocartilage Abstract Motion‐based therapies have been applied to promote healing of arthritic joints. The goal of the current study was to determine the early molecular events that are responsible for the beneficial actions of motion‐based therapies on meniscal fibrocartilage. Rabbit knees with Antigen‐Induced‐Arthritis (AIA) were exposed to continuous passive motion (CPM) for 24 or 48 h and compared to immobilized knees. The menisci were harvested and glycosaminoglycans (GAG), interleukin‐1β (IL‐1β), matrix metalloproteinase‐1 (MMP‐1), cyclooxygenase‐2 (COX‐2), and interleukin‐10 (IL‐10) were determined by histochemical analysis. Within 24 h, immobilized knees exhibited marked GAG degradation. The expression of proinflammatory mediators MMP‐1, COX‐2, and IL‐1β was notably increased within 24 h and continued to increase during the next 24 h in immobilized knees. Knees subjected to CPM revealed a rapid and sustained decrease in GAG degradation and the expression of all proinflammatory mediators during the entire period of CPM treatment. More importantly, CPM induced synthesis of the anti‐inflammatory cytokine IL‐10. The results demonstrate that mechanical signals generated by CPM exert potent anti‐inflammatory signals on meniscal fibrochondrocytes. Furthermore, these studies explain the molecular basis of the beneficial effects of CPM observed on articular cartilage and suggest that CPM suppresses the inflammatory process of arthritis more efficiently than immobilization. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Journal of Orthopaedic Research - Tập 23 - Trang 1165-1171 - 2005
Why would cement porosity reduction be clinically irrelevant, while experimental data show the contrary Abstract Laboratory bench tests have shown that porosity reduction increases the fatigue life of bone cement specimens. Clinically, however, the effect porosity reduction is subject to debate. We hypothesized that the discrepancy between clinical and experimental findings is related to differences in the stress distribution, which is typically uniform in experimental test specimens, while stress concentrations exist in cement around hip implants. We simulated fatigue failure of cement in a finite element model of an experimental test specimen and of a transverse slice of a total hip arthroplasty with a sharp‐cornered stem. Four levels of porosity were introduced. In the fatigue test specimen model, the fatigue life clearly was dependent on the level of porosity, while in the transverse slice model, the level of porosity had virtually no effect on failure of the cement mantle. The results of the simulations confirmed our hypothesis. In simulations of laboratory tests, pores clearly acted as crack initiators, while in the simulation of a real total hip reconstruction, crack formation was governed by local stress singularities. This explains why the beneficial effect of cement porosity reduction on the lifetime of total hip reconstructions may be hard to detect clinically. © 2005 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Journal of Orthopaedic Research - Tập 23 - Trang 691-697 - 2005
Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor‐β1 in monolayer and insulin‐like growth factor‐I in a three‐dimensional matrix Abstract This study evaluated chondrogenesis of mesenchymal progenitor stem cells (MSCs) cultured initially under pre‐confluent monolayer conditions exposed to transforming growth factor‐β (TGF‐β), and subsequently in three‐dimensional cultures containing insulin‐like growth factor I (IGF‐I). Bone marrow aspirates and chondrocytes were obtained from horses and cultured in monolayer with 0 or 5 ng of TGF‐β1 per ml of medium for 6 days. TGF‐β1 treated and untreated cultures were distributed to three‐dimensional fibrin disks containing 0 or 100 ng of IGF‐I per ml of medium to establish four treatment groups. After 13 days, cultures were assessed by toluidine blue staining, collagen types I and II in situ hybridization and immunohistochemistry, proteoglycan production by [Chondrocytic differentiation of mesenchymal stem cells sequentially exposed to transforming growth factor‐β1 in monolayer and insulin‐like growth factor‐I in a three‐dimensional matrix35 S]‐sulfate incorporation, and disk DNA content by fluorometry. Mesenchymal cells in monolayer cultures treated with TGF‐β1 actively proliferated for the first 4 days, developed cellular rounding, and formed cell clusters. Treated MSC cultures had a two‐fold increase in medium proteoglycan content. Pretreatment of MSCs with TGF‐β1 followed by exposure of cells to IGF‐I in three‐dimensional culture significantly increased the formation of markers of chondrocytic function including disk proteoglycan content and procollagen type II mRNA production. However, proteoglycan and procollagen type II production by MSC's remained lower than parallel chondrocyte cultures. MSC pretreatment with TGF‐β1 without sequential IGF‐I was less effective in initiating expression of markers of chondrogenesis. This study indicates that although MSC differentiation was less than complete when compared to mature chondrocytes, chondrogenesis was observed in IGF‐I supplemented cultures, particularly when used in concert with TGF‐β1 pretreatment. © 2001 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Journal of Orthopaedic Research - Tập 19 - Trang 738-749 - 2001
Kinematics of the knee at high flexion angles: An in vitro investigation Abstract Restoration of knee function after total knee, meniscus, or cruciate ligament surgery requires an understanding of knee behavior throughout the entire range of knee motion. However, little data are available regarding knee kinematics and kinetics at flexion angles greater than 120° (high flexion). In this study, 13° cadaveric human knee specimens were tested using an in vitro robotic experimental setup. Tibial anteroposterior translation and internal–external rotation were measured along the passive path and under simulated muscle loading from full extension to 150° of flexion. Anterior tibial translation was observed in the unloaded passive path throughout, with a peak of 31.2 ± 13.2 mm at 150°. Internal tibial rotation increased with flexion to 150° on the passive path to a maximum of 11.1 ± 6.7°. The simulated muscle loads affected tibial translation and rotation between full extension and 120° of knee flexion. Interestingly, at high flexion, the application of muscle loads had little effect on tibial translation and rotation when compared to values at 120°. The kinematic behavior of the knee at 150° was markedly different from that measured at other flexion angles. Muscle loads appear to play a minimal role in influencing tibial translation and rotation at maximal flexion. The results imply that the knee is highly constrained at high flexion, which could be due in part to compression of the posterior soft tissues (posterior capsule, menisci, muscle, fat, and skin) between the tibia and the femur. © 2003 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Journal of Orthopaedic Research - Tập 22 - Trang 90-95 - 2004
Age dependence of expression of growth factor receptors in porcine ACL fibroblasts Abstract Tissue engineering approaches that harness the stimulatory power of platelet‐rich plasma have produced encouraging results in anterior cruciate ligament (ACL) repair. However, a number of recent studies have demonstrated age‐dependent differences in cellular responses to such an approach. Identifying the reasons for these differences would allow counteracting them and consequently improve outcomes. In this study we hypothesized that these age‐related effects are caused by differences in the expression of the receptors for growth factors released from platelet‐rich plasma (PRP). Porcine ACL fibroblasts from a predetermined number of animals of different ages were obtained, and mRNA levels of the receptors of platelet‐derived growth factor (PDGF), transforming growth factor β (TGF‐β), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) were determined. Expression levels were compared across age groups (young and adolescent) and regressed on age in days. While no significant difference was seen across groups, the regression analysis showed decreases in receptor expression with increasing age. These differences were statistically significant for TGF‐β receptor 1, FGF receptor, and VEGF receptor 2; and borderline significant for TGF‐β receptor 3 and PDGF receptor. The only receptor that was not associated with age was VEGF receptor 1, a regulator of VEGF receptor 2. These findings suggest that the decrease in growth factor receptor expression as a likely reason for reduced PRP action with increasing age. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1107–1112, 2010
Journal of Orthopaedic Research - Tập 28 Số 8 - Trang 1107-1112 - 2010
Animal models for studying the etiology and treatment of low back pain ABSTRACT Chronic low back pain is a major cause of disability and health care costs. Effective treatments are inadequate for many patients. Animal models are essential to further understanding of the pain mechanism and testing potential therapies. Currently, a number of preclinical models have been developed attempting to mimic aspects of clinical conditions that contribute to low back pain (LBP). This review focused on describing these animal models and the main behavioral tests for assessing pain in each model. Animal models of LBP can be divided into the following five categories: Discogenic LBP, radicular back pain, facet joint osteoarthritis back pain, muscle‐induced LBP, and spontaneous occurring LBP models. These models are important not only for enhancing our knowledge of how LBP is generated, but also for the development of novel therapeutic regimens to treat LBP in patients. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1305–1312, 2018.
Journal of Orthopaedic Research - Tập 36 Số 5 - Trang 1305-1312 - 2018
Inhibiting IL‐1 signaling pathways to inhibit catabolic processes in disc degeneration ABSTRACT Intervertebral disc degeneration is characterized by an imbalance between catabolic and anabolic signaling, with an increase in catabolic cytokines particularly IL‐1β, a key regulator of IVD degeneration. This study aimed to investigate intracellular signaling pathways activated by IL‐1β, and GDF‐5 in the degenerate IVD to identify potential new therapeutic targets. Human NP cells were cultured in alginate beads to regain in vivo phenotype prior to stimulation with IL‐1β or GDF‐5 for 30 min, a proteasome profiler array was initially utilized to screen activation status of 46 signaling proteins. Immunoflourescence was used to investigate activation of the NFκB pathway. Cell‐based ELISAs were then deployed to confirm results for ERK1/2, p38 MAPK, c‐jun, and IκB signaling. IHC was utilized to investigate native activation status within human IVD tissue between grades of degeneration. Finally, cells were stimulated with IL‐1β in the absence or presence of p38 MAPK, c‐jun, JNK, and NFκB inhibitors to investigate effects on MMP3, MMP13, IL‐1β, IL‐6, and IL‐8 mRNA expression. This study demonstrated three key signaling pathways which were differentially activated by IL‐1β but not GDF‐5; namely p38 MAPK, c‐jun, and NFκB. While ERK 1/2 was activated by both GDF‐5 and IL‐1. Immunohistochemistry demonstrated p38 MAPK, c‐jun, and NFκB were activated during human IVD degeneration and inhibition of these pathways reduced or abrogated the catabolic effects of IL‐1β, with inhibition of NFκB signaling demonstrating most widespread inhibition of IL‐1β catabolic effects. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:74–85, 2017.
Journal of Orthopaedic Research - Tập 35 Số 1 - Trang 74-85 - 2017
Effects of material properties of femoral hip components on bone remodeling Abstract Bone loss around femoral hip stems is one of the problems threatening the long‐term fixation of uncemented stems. Many believe that this phenomenon is caused by reduced stresses in the bone (stress shielding). In the present study the mechanical consequences of different femoral stem materials were investigated using adaptive bone remodeling theory in combination with the finite element method. Bone‐remodeling in the femur around the implant and interface stresses between bone and implant were investigated for fully bonded femoral stems. Cemented stems (cobalt‐chrome or titanium alloy) caused less bone resorption and lower interface stresses than uncemented stems made from the same materials. The range of the bone resorption predicted in the simulation models was from 23% in the proximal medial cortex surrounding the cemented titanium alloy stem to 76% in the proximal medial cortex around the uncemented cobalt‐chrome stem. Very little bone resorption was predicted around a flexible, uncemented “iso‐elastic” stem, but the proximal interface stresses increased drastically relative to the stiffer uncemented stems composed of cobalt‐chrome or titanium alloy. However, the proximal interface stress peak was reduced and shifted during the adaptive remodeling process. The latter was found particularly in the stiffer uncemented cobalt‐chrome‐molybdenum implant and less for the flexible isoelastic implant.
Journal of Orthopaedic Research - Tập 10 Số 6 - Trang 845-853 - 1992
The effect of bone microstructure on the initiation and growth of microcracks Abstract Osteonal bone is often compared to a composite material and to metals as discontinuities within the material may provide sites of stress concentration for crack initiation and serve as barriers to crack growth. However, little experimental data exist to back up these hypotheses. Fluorescent chelating agents were applied at specific intervals to bone specimens fatigue tested in cyclic compression at a stress range of 80 MPa. The failed specimens were sectioned and labelled microcracks identified using UV epifluorescence microscopy. Microcrack lengths were measured and their relationship to cement lines surrounding secondary osteons recorded. Microcrack length at the time of encountering a cement line was also measured. Microcracks of less than 100 μm stopped growing when they encountered a cement line. Microcracks of greater than 100 μm in length continued to grow after encountering a cement line surrounding an osteon. Only microcracks greater than 300 μm in length were capable of penetrating osteons and these microcracks were the only ones which were observed to cause failure in the specimen. These experimental data support the hypothesis that secondary osteons act as barriers to crack propagation in compact bone. However, it shows that this microstructural barrier effect is dependent on the crack length at the time of encountering an osteon. For the vast majority of cracks, osteons act as barriers to growth but for the minority of cracks that are long enough and do break through the cement line, an osteon may actually act as a weakness in the bone and facilitate crack propagation. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Journal of Orthopaedic Research - Tập 23 Số 2 - Trang 475-480 - 2005
Bone maintenance and remodeling: A control system based on fatigue damage Abstract This paper explores the relationship between damage, repair, and remodeling in compact bone. A model of microcrack growth is developed that takes account of recent findings on the behaviour of small fatigue cracks in other materials. This is combined with a simple model of a repair process, envisaged as a constant rate of decrease in crack length. The system that results is capable of achieving a stable and precise control of crack length without the need to measure it. This is very useful because it implies that bone does not require the complexities of crack‐measuring, transducers or active decision‐making processes. A simple explanation is suggested for the presence of a “lazy zone” of remodeling equilibrium strains, and the limits of this zone are quantified. The model is developed through a necessarily simplified geometry and loading scheme but can be extended to provide a general solution applicable to in vivo conditions.
Journal of Orthopaedic Research - Tập 15 Số 4 - Trang 601-606 - 1997
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