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Weightbearing computed tomography (WBCT) enables visualization of the foot and ankle as patients stand under load. Clinical measurements of WBCT images are generally limited to two‐dimensions, which reduces the ability to quantify complex morphology of individual osseous structures as well as the alignment between two or more bones. The shape and orientation of the healthy/normal subtalar joint, in particular, is not well‐understood, which makes it very difficult to diagnose subtalar pathoanatomy. Herein, we employed statistical shape modeling to evaluate three‐dimensional (3D) shape variation, coverage, space, and congruency of the subtalar joint using WBCT data of 27 asymptomatic healthy individuals. The four most relevant findings were: (A) talar and calcaneal anatomical differences were found regarding the presence of (a) the talar posterior process, (b) calcaneal pitch, and (c) curvature of the calcaneal posterior facet; (B) the talar posterior facet articular surface area was significantly greater than the calcaneal posterior facet articular surface area; (C) the posterior facet varied in joint space distance, whereas the anteromedial facet was even; and (D) the posterior and anteromedial facet of the subtalar joint was consistently congruent. Despite considerable shape variation across the population, the posterior and anteromedial articular facets of the subtalar joint were consistently congruent. Results provide a detailed 3D analysis of the subtalar joint under a weightbearing condition in a healthy population which can be used for comparisons to pathological patient populations. The described SSM approach also shows promise for clinical evaluation of the subtalar joint from 3D surface reconstructions of WBCT images. [ABSTRACT FROM AUTHOR]

Evaluation of the subtalar joint using conventional radiographs is difficult. The purpose of this study was to assess how the posterior facet of the subtalar joint is projected on eight standard radiographic views of the foot and ankle. Weightbearing computed tomography (CT) scans of 27 volunteers without ankle pathology were performed. Eight standard views of the foot and ankle (antero‐posterior [AP] view, mortise view, subtalar view, four different Broden views) were reconstructed using digitally reconstructed radiographs (DRRs). The appearance of the posterior facet of the subtalar joint was assessed for each view. In addition, the position of the joint line was projected onto three‐dimensional (3‐D) models of the calcaneus. We found (i) on the AP view of the ankle joint, the posterior part of the posterior facet is visualized and appears convex (calcaneal side); (ii) on the mortise view of the ankle joint, a slightly more anterior part (compared to the AP view) is visualized and appears either convex or flat; (iii) on the subtalar view, the anterior part of the posterior facet is visualized and appears either convex, flat or concave; and (iv) using the Broden views, the posterior and anterior part of the posterior facet can be visualized. This study clarifies which parts of the posterior facet of the subtalar joint are visualized on eight standard views of the foot and ankle. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Orthopaedic research, and biomedical research in general, has made enormous strides to develop treatments for conditions long thought to be inevitable or untreatable; however, there is growing concern about the quality of published research. Considerable efforts have been made to improve overall research quality, integrity, and rigor, including meaningful proposals focused on transparency of reporting, appropriate use of statistics, and reporting of negative results. However, we believe that there is another key component to rigor and reproducibility that is not discussed sufficiently—analytical validation and quality control (QC). In this commentary, we discuss QC and method validation principles and practices that are systematically applied in the clinical laboratory setting to verify and monitor the analytical performance of quantitative assays, and the utility of applying similar practices to biochemical assays in the orthopaedic research setting. This commentary includes (1) recommendations for validation and QC practices, including examples of assay performance limitations uncovered by validation experiments performed in our laboratory, and (2) a description of an ongoing QC program developed to monitor the ongoing performance of commonly used assays in our lab. We hope that this commentary and the examples presented here will be thought‐provoking and inspire further discussion and adaptation of analytical validation and QC procedures to advance our shared pursuit of high‐quality, rigorous, and reproducible orthopaedic research. [ABSTRACT FROM AUTHOR]

ABSTRACT Cartilage degeneration with osteoarthritis (OA) is believed to involve the activities of interleukin-1 (IL-1), which exists as alpha and beta isoforms. The goal of this study was to measure the concentrations of both isoforms of IL-1 in the synovial fluid of normal and spontaneously osteoarthritic porcine knees, and to test the hypothesis that physiologic concentrations of IL-1α and IL-1β exhibit different potencies in activating calcium signaling, the production of matrix metalloproteinases and nitric oxide, and the loss of proteoglycans and tissue mechanical properties in cartilage and meniscus. Median concentrations of IL-1α were 0.043 ng/ml with mild OA and 0.288 ng/ml with moderate OA, whereas IL-1β concentrations were 0.109 ng/ml with mild OA and 0.122 ng/ml with moderate OA. Both isoforms induced calcium signaling in chondrocytes and meniscal cells at all concentrations. Overall, cartilage and meniscus catabolism was significantly more sensitive to IL-1α than IL-1β at concentrations of 1 ng/ml or less, while few differences were observed between the two forms at 10 ng/ml. These data provide a range of physiologic IL-1 concentrations that can serve as a framework for the comparison of various in vitro studies, as well as providing further insight for the development of anti-cytokine therapies for OA. © 2013 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 31:1039-1045, 2013 [ABSTRACT FROM AUTHOR]

The multidirectional biomechanics of the thumb carpometacarpal (CMC) joint underlie the remarkable power and precision of the thumb. Because of the unconfined nature of thumb CMC articulation, these biomechanics are largely dictated by ligaments, notably the anterior oblique ligament (AOL) and the dorsoradial ligament (DRL). However, the rotational and translational stabilizing roles of these ligaments remain unclear, as evidenced by the variety of interventions employed to treat altered pathological CMC biomechanics. The purpose of this study was to determine the effects of sectioning the AOL (n = 8) or DRL (n = 8) on thumb CMC joint biomechanics (rotational range‐of‐motion [ROM] and stiffness, translational ROM) in 26 rotational directions, including internal and external rotation, and in eight translational directions. Using a robotic musculoskeletal simulation system, the first metacarpal of each specimen (n = 16) was rotated and translated with respect to the trapezium to determine biomechanics before and after ligament sectioning. We observed the greatest increase in rotational ROM and decrease in rotational stiffness in flexion directions and internal rotation following DRL transection and in extension directions following AOL transection. The greatest increase in translational ROM was in dorsal and radial directions following DRL transection and in volar directions following AOL transection. These data suggest the AOL and DRL play complementary stabilizing roles, primarily restraining translations in the direction of and rotations away from the ligament insertion sites. These findings may inform future interventions or implant designs for pathological CMC joints. [ABSTRACT FROM AUTHOR]

Our objective was to characterize variations in mechanical knee alignment, tibial torsion, tibial width, and ACL laxity measurements between Japanese and Caucasian populations in the healthy, young adult knee joint. Seventy young adult subjects participated in this study, including 23 Japanese and 47 Caucasian subjects. Coronal magnetic resonance images of the hip, knee, and ankle were acquired for analysis. Japanese subjects had a significantly higher ( p = 0.04) varus alignment (1.64 ± 0.43° standard error) than Caucasians (0.55 ± 0.33°), while women exhibited a more valgus alignment (0.16 ± 0.52°) than men (0.94 ± 0.42°, p = 0.04). Significant differences were found in tibial torsion and ACL laxity ( p < 0.01) between ethnicities, with Japanese exhibiting lower tibial torsion (33.4 ± 10.0°) and higher ACL laxity (7.5 ± 0.4 mm) measurements compared to Caucasians (38.9 ± 9.5° and 5.7 ± 0.3 mm, respectively). Significant differences between genders were found in hip-knee-ankle alignment ( p = 0.04), tibial width ( p < 0.0001), and ACL laxity ( p < 0.01) measurements. Measurements were reliable between observers and for repeated positioning. Our study provides new insight into anatomical and geometric differences in the knee joint between Japanese and Caucasians, as well as between females and males. Further consideration of these results may improve development of implants to accommodate for these differences, and understanding of characteristics leading to increased prevalence of knee OA in certain populations. The use of magnetic resonance imaging to obtain these measurements also allows soft tissue structure characterization without exposure to ionizing radiation. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Despite decades of research since its first description, subtalar joint instability remains a diagnostic enigma within the concept of hindfoot instability. This could be attributed to current imaging techniques, which are impeded by two‐dimensional measurements. Therefore, we used weightbearing computed tomography imaging to quantify three‐dimensional displacement associated with subtalar joint instability. Three‐dimensional models were generated in seven paired cadaver specimens to compute talocalcaneal displacement after different patterns of axial load (85 kg) combined with torque in internal and external rotation (10 Nm). Sequential imaging was repeated in the subtalar joint containing intact ligaments to determine reference displacement. Afterward, the interosseus talocalcaneal ligament (ITCL) or calcaneofibular ligament (CFL) was sectioned, then the ITCL with CFL and after the ITCL, CFL with the deltoid ligament (DL). The highest translation could be detected in the dorsal direction and the highest rotation occurred in the internal direction when external torque was applied to the foot without load. These displacements differed significantly from the condition containing intact ligaments, with a mean difference of 1.6 mm (95% CI, 1.3 to 1.9) for dorsal translation and a mean of 12.4° (95% CI, 10.1 to 14.8) for internal rotation. Clinical relevance: Our study provides a novel and noninvasive analysis to quantify subtalar joint instability based on three‐dimensional WBCT imaging. This approach overcomes former studies using trans‐osseous fixation to determine three‐dimensional subtalar joint displacement and implements an imaging device and software modalities that are readily available. Based on our findings, we recommend applying torque in external rotation to the foot to optimize the detection of subtalar joint instability. [ABSTRACT FROM AUTHOR]

Progressive collapsing foot deformity (PCFD) is characterized by a progressive subluxation of the peritalar bones and respective joints. Two‐dimensional conventional radiographs are limited in their ability to visualize the peritalar bones and joints with adequate detail to describe the complex three‐dimensional deformity. An improved understanding of the relationship between joint coverage and deformity would allow clinicians to use coverage analysis to distinguish among the stages of PCFD. The aim of this study was to analyze the joint coverage of the six articular relationships within the talocrural, subtalar, and Chopart joints using weightbearing computed tomography (WBCT) scans. Ten individuals with a flexible hindfoot and ten individuals with a rigid hindfoot presentation of PCFD were compared to twenty‐seven asymptomatic control individuals. The three most relevant findings are: (I) the anterior‐medial facet of the subtalar joint contains the greatest reduction in coverage for patients with a rigid deformity, (II) an increase in talonavicular overlap (TNO) moderately correlated with a decreased coverage in the: tibiotalar, anterior‐medial subtalar, talonavicular joints, and (III) the calcaneocuboid joint lacks radiographic values to adequately quantify alignment and coverage. To conclude, there were significant differences in coverage area of various articulating regions throughout the hind‐ and midfoot when comparing PCFD patients to asymptomatic control individuals. Relevant radiographic measures correlating to articular coverage areas of clinical interest were identified, possibly helping to better quantify PCFD in clinical practice. [ABSTRACT FROM AUTHOR]

ABSTRACT Little is known about knee-specific factors that influence contact mechanics. Finite Element (FE) models offer a powerful tool to study contact mechanics, but there often exists ambiguity in the exact values of the inputs (e.g., tissue properties), which can result in a range of output values. Our objective was to quantify the reduction in the range of output values (defined herein as 'uncertainty') from FE models of the human knee joint when known pre-defined values are used for clinically measurable inputs. To achieve this goal, we applied a statistically augmented FE approach to three human cadaveric knees for which full geometric and kinematic data were available. Two sets of conditions were simulated: All model inputs, clinically measurable or not, were varied to represent a 'normal' patient population (Condition 1); subsets of clinically measurable variable inputs were fixed at specific values (called 'patient derived inputs,' or PDIs) while the other variables were varied over 'normal' values (Condition 2). We found that by fixing body mass index and the anterior-posterior position of the meniscal-bony insertion points, model output uncertainty was reduced by one- to three-fifths. The magnitude of uncertainty reduction was strongly influenced by the individual knee. It was observed that knees with great anterior-posterior translation during gait had greater reductions in uncertainty when PDIs were used. This study represents the first step in developing FE models of the human knee joint based on inputs that can be derived from patients in a clinical setting. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2233-2242, 2017. [ABSTRACT FROM AUTHOR]

Cam‐type femoroacetabular impingement (FAI) syndrome is a painful, structural hip disorder. Herein, we investigated hip joint mechanics through in vivo, dynamic measurement of the bone‐to‐bone distance between the femoral head and acetabulum in patients with cam FAI syndrome and morphologically screened controls. We hypothesized that individuals with cam FAI syndrome would have larger changes in bone‐to‐bone distance compared to the control group, which we would interpret as altered joint mechanics as signified by greater movement of the femoral head as it articulates within the acetabulum. Seven patients with cam FAI syndrome and 11 asymptomatic individuals with typical morphology underwent dual fluoroscopy imaging during level and inclined walking (upward slope). The change in bone‐to‐bone distance between femoral and acetabular bone surfaces was evaluated for five anatomical regions of the acetabulum at each timepoint of gait. Linear regression analysis of the bone‐to‐bone distance considered two within‐subject factors (activity and region) and one between‐subjects factor (group). Across activities, the change in minimum bone‐to‐bone distance was 1.38–2.54 mm for the cam FAI group and 1.16–1.84 mm for controls. In all regions except the anterior–superior region, the change in bone‐to‐bone distance was larger in the cam group than the control group (p ≤ 0.024). An effect of activity was detected only in the posterior–superior region where larger changes were noted during level walking than incline walking. Statement of clinical significance: Patients with cam FAI syndrome exhibit altered hip joint mechanics during the low‐demand activity of walking; these alterations could affect load transmission, and contribute to pain, tissue damage, and osteoarthritis. [ABSTRACT FROM AUTHOR]

Injuries to the Lisfranc complex may require surgical fixation, the stability of which may be correlated with bone mineral density (BMD). However, there is limited research on regional BMD variations in the Lisfranc complex. This study used quantitative micro‐CT to characterize regional BMD in the four bones (medial cuneiform, intermediate cuneiform, first metatarsal, and second metatarsal) of this complex. Twenty‐four cadaveric specimens were imaged with a calibration phantom using micro‐CT. Each bone was segmented and divided into eight regions based on an anatomical coordinate system. BMD for each octant was calculated using scan‐specific calibration equations and average image intensity. Differences between regions were analyzed using ANOVA with post hoc analysis and differences between groups of four octants in each plane were analyzed with t‐tests with significance level α = 0.05. The highest density region in the medial cuneiform was the distal–dorsal–lateral and dorsal regions showed significantly higher BMD than plantar regions. The intermediate cuneiform had the highest density in the distal–dorsal–medial region and the dorsal and medial regions had higher BMD than the plantar and lateral regions, respectively. The densest region of the first metatarsal was the distal–dorsal–lateral and distal regions had significantly higher BMD than proximal regions. In the second metatarsal, the distal–dorsal–medial region had the highest density, and the distal, dorsal, and medial regions had significantly higher BMD than the proximal, plantar, and lateral regions, respectively. The predominant finding was a pattern of increased density in the dorsal bone regions, which may be relevant in the surgical management of Lisfranc injuries. [ABSTRACT FROM AUTHOR]

Meniscus injuries are common and a major cause of long‐term joint degeneration and disability. Current treatment options are limited, so novel regenerative therapies or tissue engineering strategies are urgently needed. The development of new therapies is hindered by a lack of knowledge regarding the cellular biology of the meniscus and a lack of well‐established methods for studying meniscus cells in vitro. The goals of this study were to (1) establish baseline expression profiles and dedifferentiation patterns of inner and outer zone primary meniscus cells, and (2) evaluate the utility of poly(ethylene glycol) diacrylate (PEGDA) and gelatin methacrylate (GelMA) polymer hydrogels to reverse dedifferentiation trends for long‐term meniscus cell culture. Using reverse transcription‐quantitative polymerase chain reaction, we measured expression levels of putative meniscus phenotype marker genes in freshly isolated meniscus tissue, tissue explant culture, and monolayer culture of inner and outer zone meniscus cells from porcine knees to establish baseline dedifferentiation characteristics, and then compared these expression levels to PEGDA/GelMA embedded passaged meniscus cells. COL1A1 showed robust upregulation, while CHAD, CILP, and COMP showed downregulation with monolayer culture. Expression levels of COL2A1, ACAN, and SOX9 were surprisingly similar between inner and outer zone tissue and were found to be less sensitive as markers of dedifferentiation. When embedded in PEGDA/GelMA hydrogels, expression levels of meniscus cell phenotype genes were significantly modulated by varying the ratio of polymer components, allowing these materials to be tuned for phenotype restoration, meniscus cell culture, and tissue engineering applications. [ABSTRACT FROM AUTHOR]

Abstract: Although the rabbit hindlimb has been commonly used as an experimental animal model for studies of osteoarthritis, bone growth and fracture healing, the in vivo biomechanics of the rabbit knee joint have not been quantified. The purpose of this study was to investigate the kinematic and kinetic patterns during hopping of the adult rabbit, and to develop a model to estimate the joint contact force distribution between the tibial plateaus. Force platform data and three-dimensional motion analysis using infrared markers mounted on intracortical bone pins were combined to calculate the knee and ankle joint intersegmental forces and moments. A statically determinate model was developed to predict muscle, ligament and tibiofemoral joint contact forces during the stance phase of hopping. Variations in hindlimb kinematics permitted the identification of two landing patterns, that could be distinguished by variations in the magnitude of the external knee abduction moment. During hopping, the prevalence of an external abduction moment led to the prediction of higher joint contact forces passing through the lateral compartment as compared to the medial compartment of the knee joint. These results represent critical data on the in vivo biomechanics of the rabbit knee joint, which allow for comparisons to both other experimental animal models and the human knee, and may provide further insight into the relationships between mechanical loading, osteoarthritis, bone growth, and fracture healing. [Copyright &y& Elsevier]

ABSTRACT: The objective of this study was to investigate the expression of the chemokine CXCL10 and its role in joint tissues following articular fracture. We hypothesized that CXCL10 is upregulated following articular fracture and contributes to cartilage degradation associated with post‐traumatic arthritis (PTA). To evaluate CXCL10 expression following articular fracture, gene expression was quantified in synovial tissue from knee joints of C57BL/6 mice that develop PTA following articular fracture, and MRL/MpJ mice that are protected from PTA. CXCL10 protein expression was assessed in human cartilage in normal, osteoarthritic (OA), and post‐traumatic tissue using immunohistochemistry. The effects of exogenous CXCL10, alone and in combination with IL‐1, on porcine cartilage explants were assessed by quantifying the release of catabolic mediators. Synovial tissue gene expression of CXCL10 was upregulated by joint trauma, peaking one day in C57BL/6 mice (25‐fold) versus 3 days post‐fracture in MRL/MpJ mice (15‐fold). CXCL10 protein in articular cartilage was most highly expressed following trauma compared with normal and OA tissue. In a dose dependent manner, exogenous CXCL10 significantly reduced total matrix metalloproteinase (MMP) and aggrecanase activity of culture media from cartilage explants. CXCL10 also trended toward a reduction in IL‐1α‐stimulated total MMP activity (p = 0.09) and S‐GAG (p = 0.09), but not NO release. In conclusion, CXCL10 was upregulated in synovium and chondrocytes following trauma. However, exogenous CXCL10 did not induce a catabolic response in cartilage. CXCL10 may play a role in modulating the chondrocyte response to inflammatory stimuli associated with joint injury and the progression of PTA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1220–1227, 2018. [ABSTRACT FROM AUTHOR]

ABSTRACT The saddle-shaped trapeziometacarpal (TMC) joint contributes importantly to the function of the human thumb. A balance between mobility and stability is essential in this joint, which experiences high loads and is prone to osteoarthritis (OA). Since instability is considered a risk factor for TMC OA, we assessed TMC joint instability during the execution of three isometric functional tasks (key pinch, jar grasp, and jar twist) in 76 patients with early TMC OA and 44 asymptomatic controls. Computed tomography images were acquired while subjects held their hands relaxed and while they applied 80% of their maximum effort for each task. Six degree-of-freedom rigid body kinematics of the metacarpal with respect to the trapezium from the unloaded to the loaded task positions were computed in terms of a TMC joint coordinate system. Joint instability was expressed as a function of the metacarpal translation and the applied force. We found that the TMC joint was more unstable during a key pinch task than during a jar grasp or a jar twist task. Sex, age, and early OA did not have an effect on TMC joint instability, suggesting that instability during these three tasks is not a predisposing factor in TMC OA. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:1639-1645, 2015. [ABSTRACT FROM AUTHOR]

Posttraumatic arthritis commonly develops following articular fracture. The objective of this study was to develop a closed joint model of transarticular impact with and without creation of an articular fracture that maintains the physiologic environment during loading. Fresh intact porcine knees were preloaded and impacted at 294 J via a drop track. Osteochondral cores were obtained from the medial and lateral aspects of the femoral condyles and tibial plateau. Chondrocyte viability was assessed at days 0, 3, and 5 postimpact in sham, impacted nonfractured, and impacted fractured joints. Total matrix metalloproteinase (MMP) activity, aggrecanase (ADAMTS-4) activity, and sulfated glycosaminoglycan (S-GAG) release were measured in culture media from days 3 and 5 posttrauma. No differences were observed in chondrocyte viability of impacted nonfractured joints (95.9 ± 6.9%) when compared to sham joints (93.8 ± 7.7%). In impacted fractured joints, viability of the fractured edge was 40.5 ± 27.6% and significantly lower than all other sites, including cartilage adjacent to the fractured edge ( p < 0.001). MMP and aggrecanase activity and S-GAG release were significantly increased in specimens from the fractured edge. This study showed that joint impact resulting in articular fracture significantly decreased chondrocyte viability, increased production of MMPs and aggrecanases, and enhanced S-GAG release, whereas the same level of impact without fracture did not cause such changes. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:501-510, 2011 [ABSTRACT FROM AUTHOR]

The purpose of this study was to clarify meniscal displacement and cartilage-meniscus contact behavior in a full extension position and a deep knee flexion position. We also studied whether the meniscal translation pattern correlated with the tibiofemoral cartilage contact kinematics. Magnetic resonance (MR) images were acquired at both positions for 10 subjects using a conventional MR scanner. Subjects achieved a flexion angle averaging 139° ± 3°. Both medial and lateral menisci translated posteriorly on the tibial plateau during deep knee flexion. The posterior translation of the lateral meniscus (8.2 ± 3.2 mm) was greater than the medial (3.3 ± 1.5 mm). This difference was correlated with the difference in tibiofemoral contact kinematics between medial and lateral compartments. Contact areas in deep flexion were approximately 75% those at full extension. In addition, the percentage of area in contact with menisci increased significantly due to deep flexion. Our results related to meniscal translation and tibio-menisco-femoral contact in deep knee flexion, in combination with information about force and pressure in the knee, may lead to a better understanding of the mechanism of meniscal degeneration and osteoarthritis associated with prolonged kneeling and squatting. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:673-684, 2008 [ABSTRACT FROM AUTHOR]

Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration of the knee joint. Injured and degenerative joints are characterized by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which with prolonged exposure can induce catabolic and anti-anabolic activities that inhibit tissue repair. We used an in vitro model system to examine the hypotheses that acute exposure to IL-1 inhibits meniscal repair, and that an IL-1-mediated increase in matrix metalloproteinase (MMP) activity is associated with the inhibition of repair. Integrative tissue repair was studied between concentric explants of porcine medial menisci that were treated with IL-1α acutely (100 pg/mL for 1 or 3 days) or chronically (100 pg/mL for entire culture duration). After 14 and 28 days in culture, biomechanical testing, cell viability, and histology were performed to assess meniscal repair. Total specific MMP activity in the culture media was measured using a quenched fluorescent substrate. As little as 1 day of IL-1 exposure significantly reduced shear strength, cell accumulation, and tissue repair compared to controls. IL-1 exposure for 1 or 3 days significantly increased MMP activity that subsided by day 9. With chronic IL-1 exposure, MMP activity remained elevated for the duration of culture and was negatively correlated with repair strength. Our study shows that short-term exposure to physiologically relevant concentrations of IL-1 significantly reduces meniscal repair in vitro, and thus may potentially inhibit the intrinsic repair response in vivo. The suppression of IL-1 or MMP expression and/or activity warrant investigation as potential strategies for promoting meniscal repair. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:504-512, 2008 [ABSTRACT FROM AUTHOR]