Publications by authors named "Kristen I Barton"

16 Publications

  • Page 1 of 1

Structural Consequences of a Partial Anterior Cruciate Ligament Injury on Remaining Joint Integrity: Evidence for Ligament and Bone Changes Over Time in an Ovine Model.

Am J Sports Med 2021 03 1;49(3):637-648. Epub 2021 Feb 1.

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Canada.

Background: Severe injury to the knee joint often results in accelerated posttraumatic osteoarthritis (PTOA). In an ovine knee injury model, altered kinematics and degradation of the cartilage have been observed at 20 and 40 weeks after partial anterior cruciate ligament (ACL) transection (p-ACL Tx) surgery. However, changes to the integrity of the remaining intact intra-articular ligaments (posterolateral [PL] band and posterior cruciate ligament [PCL]) as well as the subchondral bone after anteromedial (AM) band Tx remain to be characterized.

Purpose: (1) To investigate histological alterations to the remaining intact intra-articular ligaments, the synovium, and the infrapatellar fat pad (IPFP) and (2) to quantify subchondral bone changes at the contact surfaces of the proximal tibia at 20 and 40 weeks after AM band Tx.

Study Design: Descriptive laboratory study.

Methods: Mature female Suffolk cross sheep were allocated into 3 groups: nonoperative controls (n = 6), 20 weeks after partial ACL transection (p-ACL Tx; n = 5), and 40 weeks after p-ACL Tx (n = 6). Ligament, synovium, and IPFP sections were stained and graded. Tibial subchondral bone microarchitecture was assessed using high-resolution peripheral quantitative computed tomography.

Results: p-ACL Tx of the AM band led to significant change in histological scores of the PL band and the PCL at 20 weeks after p-ACL Tx ( = .031 and = .033, respectively) and 40 weeks after p-ACL Tx ( = .011 and = .029) as compared with nonoperative controls. Alterations in inflammatory cells and collagen fiber orientation contributed to the greatest extent of the combined histological score in the PL band and PCL. p-ACL Tx did not lead to chronic activation of the synovium or IPFP. Trabecular bone mineral density was strongly inversely correlated with combined gross morphological damage in the top and middle layers of the subchondral bone in the lateral tibial plateau for animals at 40 weeks after p-ACL Tx.

Conclusion: p-ACL Tx influences the integrity (biology and structure) of remaining intact intra-articular ligaments and bone microarchitecture in a partial knee injury ovine model.

Clinical Relevance: p-ACL Tx leads to alterations in structural integrity of the remaining intact ligaments and degenerative changes in the trabecular bone mineral density, which may be detrimental to the injured athlete's knee joint in the long term.
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http://dx.doi.org/10.1177/0363546520985279DOI Listing
March 2021

Methylprednisolone acetate mitigates IL1β induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

Inflamm Res 2021 Jan 23;70(1):99-107. Epub 2020 Nov 23.

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Objective And Design: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1β induction and to assess responsiveness of the explants.

Material Or Subjects: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep.

Treatment: Methylprednisolone.

Methods: The samples were allocated into six groups: (1) control, (2) MPA (10 M), (3) MPA (10 M), (4) IL1β, (5) IL1β + 10 M MPA, or (6) IL1β + 10 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative C method.

Results: Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1β (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFβ1, TLR4, and adipose-related molecules.

Conclusions: Methylprednisolone significantly mitigated IL1β induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.
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http://dx.doi.org/10.1007/s00011-020-01421-2DOI Listing
January 2021

Five- and six-strand hamstring grafts consistently produce appropriate graft diameters for anterior cruciate ligament reconstruction.

Knee Surg Sports Traumatol Arthrosc 2021 Sep 9;29(9):2940-2947. Epub 2020 Oct 9.

International Knee and Joint Centre, Abu Dhabi, United Arab Emirates.

Purpose: Hamstring tendon graft diameter less than 8 mm has been correlated with an increased risk of anterior cruciate ligament reconstruction (ACLR) graft failure. The purpose of this study was to measure and compare the diameter of 3-, 4-, 5-, and 6-strand gracilis and semitendinosus (ST) hamstring tendon (HT) ACLR grafts, and to determine if there is a correlation between anthropometric data, HT length, and diameter of the HT ACLR graft.

Methods: Male patients (n = 78) undergoing primary or revision ACLR with a HT autograft between July 2018 and March 2020 were recruited. Pre-operative anthropometric data was collected. Gracilis and ST tendons were harvested and the length and diameter measured. The following HT graft configurations were prepared in each patient: triple ST; double gracilis + double ST; double gracilis + triple ST; triple gracilis + triple ST. Paired t-tests and Pearson's correlation coefficients were used to assess demographics, anthropometrics, graft diameter, and tendon length. A non-parametric test was used to compare femoral and tibial ACL graft diameters of the 3-, 4-, 5-, and 6-strand HT graft configurations.

Results: For the femoral end, 10%, 19%, 69% and 86% of the patients achieved graft diameters of equal to or greater than 8 mm in 3-, 4-, 5- and 6-strand HT graft configurations respectively. For the tibial end, 27%, 10%, 83%, and 92% of the patients achieved graft diameters of equal to or greater than 8 mm in 3-, 4-, 5-, and 6-strand HT graft configurations respectively. The largest increases in HT graft diameters were noted between the femoral end of 6- vs. 3-strand grafts (mean difference 1.7 ± 0.5 mm; p < 0.001) and between the tibial end of 6- vs. 4-strand grafts (mean difference 2.0 ± 0.5 mm; p < 0.001). Height and leg length were moderately positively correlated with ST tendon length (r = 0.54-0.51) and gracilis tendon length (r = 0.52-0.45), and thigh and shank lengths were moderately positively correlated with ST tendon length (r = 0.43 and 0.40, respectively).

Conclusion: Traditional 4-strand HT ACL autografts in male patients undergoing ACLR in the United Arab Emirates result in graft diameters less than 8 mm in the majority of patients.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-020-06313-wDOI Listing
September 2021

Communication in surgical decision-making while managing metastatic bone disease: matching patient expectations with surgical goals.

Support Care Cancer 2021 Feb 30;29(2):1111-1119. Epub 2020 Jun 30.

McCaig Institute for Bone & Joint Health, Cumming School of Medicine Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada.

Background: There is a paucity of research examining how surgical decision-making for metastatic bone disease (MBD) can be optimized to improve quality of life (QOL) and functional outcomes, while accurately aligning with patient goals and expectations. The objective of this study was to survey and interview patients with MBD and support persons (PS), physicians, and allied health care providers (HCP) with the goal of identifying (1) important surgical issues related to MBD management, (2) discordance in perioperative expectations, and (3) perceived measures of success in the surgical management of MBD.

Methods: Utilizing a custom survey developed by HCP and patients with MBD, participants were asked to (1) identify important issues related to MBD management, (2) rank perceived measures of success, and (3) answer open-ended questions pertaining to the management of MBD.

Results: From the survey, increased life expectancy, minimizing disease progression, removal of local tumour, timely surgery after diagnosis, increased length of hospitalization, and physiotherapy access were all identified as significant discordant goals between PS and physicians/HCP. Conversely, there was an agreement between physicians and HCP who considered improved QOL and functional outcomes as most important goals. Structured homogenous-group workshops identified the need for (1) improved discussions of prognosis, surgical options, expectations, timelines, and resources, (2) the use of a care team "quarterback", and (3) an increased use of multi-disciplinary treatment planning.

Conclusions: We feel this data highlights the importance of improved communication and coordination in treating patients with MBD. Further research evaluating how surgical techniques influence survival and disease progression in MBD is highly relevant and important to patients.
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http://dx.doi.org/10.1007/s00520-020-05595-7DOI Listing
February 2021

Molecular Response of Rabbit Menisci to Surgically Induced Hemarthrosis and a Single Intra-Articular Dexamethasone Treatment.

J Orthop Res 2019 09 20;37(9):2043-2052. Epub 2019 Jun 20.

Cumming School of Medicine, McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, Alberta, Canada.

Anterior cruciate ligament reconstructive surgery can restore biomechanical stability, however, such surgery cannot reliably prevent the onset of post-traumatic osteoarthritis. The aim of this study was to elucidate the molecular response that occurs within the menisci following a surgical injury that allows bleeding into the joint space, and then to investigate the effect of dexamethasone (DEX) on this molecular response. Cell viability studies following acute controlled exposure to blood and blood plus DEX were also conducted. Forty-eight New Zealand white rabbits were randomly allocated into control, sham, surgical, and surgical  + DEX groups (each group n  =  6). Animals were sacrificed at 48 h and 9 weeks, and menisci were harvested. The messenger RNA (mRNA) expression levels for key inflammatory, and degradative proteins, as well as mRNA levels for autophagy pathway molecules were quantified, and statistically significant changes were described. Meniscal cell viability was calculated by incubating groups of medial and lateral menisci in autologous blood, or autologous blood plus DEX for 48 h (each group n  =  4; total of eight medial and eight lateral menisci), and then conducting a histological live/dead assay. Results indicated a significant reduction in only medial meniscal cell viability when the tissue was exposed to blood in combination with DEX. A single administration of DEX following surgery significantly suppresses the elevated molecular expression for key inflammatory and degradative markers within menisci at 48 h and 9 weeks post-surgery. In vitro, autologous blood did not affect cell viability, but addition of DEX uniquely impacted the medial menisci. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2043-2052, 2019.
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http://dx.doi.org/10.1002/jor.24346DOI Listing
September 2019

Three-dimensional in vivo kinematics and finite helical axis variables of the ovine stifle joint following partial anterior cruciate ligament transection.

J Biomech 2019 May 22;88:78-87. Epub 2019 Mar 22.

McCaig Institute for Bone & Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada; Schulich School of Engineering, University of Calgary, Calgary, AB, Canada. Electronic address:

Partial anterior cruciate ligament (p-ACL) rupture is a common injury, but the impact of a p-ACL injury on in vivo joint kinematics has yet to be determined in an animal model. The in vivo kinematics of the ovine stifle joint were assessed during 'normal' gait, and at 20 and 40 weeks after p-ACL transection (Tx). Gross morphological scoring of the knee was conducted. p-ACL Tx creates significant progressive post-traumatic osteoarthritis (PTOA)-like damage by 40 weeks. Statistically significant increases for flexion angles at hoof-strike (HS) and mid-stance (MST) were seen at 20 weeks post p-ACL Tx and the HS and hoof-off (HO) points at 40 weeks post p-ACL-Tx, therefore increased flexion angles occurred during stance phase. Statistically significant increases in posterior tibial shift at the mid-flexion (MF) and mid-extension (ME) points were seen during the swing phase of the gait cycle at 40 weeks post p-ACL Tx. Correlation analysis showed a strong and significant correlation between kinematic changes (instabilities) and gross morphological score in the inferior-superior direction at 40 weeks post p-ACL Tx at MST, HO, and MF. Further, there was a significant correlation between change in gross morphological combined score (ΔGCS) and the change in location of the helical axis in the anterior direction (ΔsAP) after p-ACL Tx for all points analyzed through the gait cycle. This study quantified in vivo joint kinematics before and after p-ACL Tx knee injury during gait, and demonstrated that a p-ACL knee injury leads to both PTOA-like damage and kinematic changes.
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http://dx.doi.org/10.1016/j.jbiomech.2019.03.021DOI Listing
May 2019

Alterations in Joint Angular Velocity Following Traumatic Knee Injury in Ovine Models.

Ann Biomed Eng 2019 Mar 17;47(3):790-801. Epub 2019 Jan 17.

McCaig Institute for Bone & Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Little effort has been directed towards the consequence of an injury on joint angular velocity. We hypothesized that the magnitude of knee joint angular velocity would be decreased after injury. Four injury groups were investigated in an ovine model: (1) anterior cruciate ligament (ACL) and medial collateral ligament (MCL) transection (ACL/MCL Tx) (n = 5), (2) lateral meniscectomy (Mx) (n = 5), (3) partial ACL transection (p-ACL Tx) (n = 5), and (4) partial-ACL and MCL transection (p-ACL/MCL Tx) (n = 5). The magnitude of the angular velocities decreased in the subjects of all groups at multiple points of the gait cycle. The maximum angular velocities during stance and the maximum extension angular velocities during swing were decreased in 15/20 and 17/20 subjects, respectively. There were strong correlations between morphological osteoarthritis scores and the reduction in the maximum extension angular velocities during swing 40 weeks post-p-ACL Tx and 20 weeks post-ACL/MCL Tx. There was no correlation between the decrease of the angular velocity and morphological osteoarthritis scores in the Mx group and the p-ACL/MCL Tx group. The reduction in angular velocity may be a helpful addition as a surrogate measure of OA risk after ACL injury, and could have clinical significance after further investigation in humans.
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http://dx.doi.org/10.1007/s10439-019-02203-6DOI Listing
March 2019

Scientific overview on CSCI-CITAC Annual General Meeting and 2017 Young Investigators' Forum.

Clin Invest Med 2018 10 5;41(3):E156-E164. Epub 2018 Oct 5.

Cumming School of Medicine, University of Calgary, Calgary, AB.

The 2017 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national Annual General Meeting (AGM) held in Toronto, Ontario November 20-22, 2017, in conjunction with the University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Roll up your sleeves-How to manage your physician scientist career", emphasizing lectures and workshops that were designed to provide tools for being proactive and successful in career planning. The keynote speakers were Dr. Rod McInnes (McGill University and Canadian Institutes of Health Research Acting President), who was the Distinguished Scientist Award recipient, Dr. David Goltzman (McGill University), who was the 2017 Henry Friesen Award recipient, Dr. Gillian Hawker (University of Toronto), Dr. Mike Sapieha (Université de Montréal), who was the 2017 Joe Doupe Award recipient, and Dr. Alex MacKenzie (Children's Hospital of Eastern Ontario Research Institute, University of Ottawa). The workshops, focusing on career development for clinician scientists, were hosted by Dr. Lisa Robinson, Dr. Nicola Jones, Kevin Vuong, Fran Brunelle, Dr. Jason Berman and Dr. Alan Underhill. Further to this, the Young Investigators' Forum encompasses presentations from scientist-clinician trainees from across the country. All scientific abstracts are summarized in this review. There were over 100 abstracts showcased at this year's meeting during the highlighted poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.
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http://dx.doi.org/10.25011/cim.v41i3.31020DOI Listing
October 2018

The Need for an Executive Leadership Curriculum in Scientist-Clinician Training Programs.

Clin Invest Med 2018 09 30;41(3):E144-E147. Epub 2018 Sep 30.

Leaders in Medicine Program, Cumming School of Medicine, University of Calgary; Undergraduate Medical Education, Cumming School of Medicine, University of Calgary.

The health of Canadians depends on effective leadership among health care providers to facilitate the translation of new health discoveries into clinical practice. Clinician-scientists play an important role in bridging the gap between research and clinical practice, and require effective leadership skills to advance clinical practice successfully. To accelerate the leadership development in clinician scientist trainees, with the aim of developing strong leaders in administration and health advocacy, the Leaders in Medicine (LIM) training program at the University of Calgary created an Executive Leadership Coaching Program involving three phases: 1) an evidence-based evaluation tool, the Core Values IndexTM (CVI), that was used to identify the key drivers behind how individuals can be most effective in making their contribution; 2) small group workshops to debrief the results of the CVI assessment; and 3) one-on-one executive coaching sessions to facilitate the discovery, development and deployment of individual leadership capabilities. Coaching in leadership strategies enables clinician-scientist trainees to lead, influence, manage and deliver science-based improvements into the practice of medicine. We strongly recommend that other Canadian scientist-clinician training programs consider opportunities like the ones we offer to our LIM trainees. This training has important implications for the delivery of healthcare in Canada.
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http://dx.doi.org/10.25011/cim.v41i3.30855DOI Listing
September 2018

Newsletter Fall 2018:  Clinician Investigator Trainee Association of Canada (CITAC).

Clin Invest Med 2018 09 18;41(3):E127-E129. Epub 2018 Sep 18.

Cumming School of Medicine, University of Calgary, Calgary, AB.

Message from the President: Optimism for the Future The Clinician-Investigator Trainee Association of Canada (CITAC) was established in 2006 to address issues relevant to Canadian trainees seeking dual training in medicine and research. As clinician-investigator (CI) trainees, we comprise but a fraction (less than 5%) of all medical trainees. Our 'bilingual' careers render our individual paths less straightforward and more challenging. As a community, we have had to confront several disappointments, perhaps most notably the cessation of funding support for MD/PhD programs in 2015, previously offered by the Canadian Institutes of Health Research (CIHR). Despite these individual and collective challenges, I remain optimistic and incredibly excited about our future. In my own work, I am reminded constantly that being trusted with the dual responsibility of patient care and innovation in medicine is a privilege to be cherished, rather than a burden to be feared. That which makes our path doubly challenging also makes it doubly rewarding. The progress that CITAC has made over the years only adds to my optimism, and I wish to take this opportunity to remind you of how far we have come and how much further we hope to go.
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http://dx.doi.org/10.25011/cim.v41i3.30702DOI Listing
September 2018

Posttraumatic Osteoarthritis Development and Progression in an Ovine Model of Partial Anterior Cruciate Ligament Transection and Effect of Repeated Intra-articular Methylprednisolone Acetate Injections on Early Disease.

Am J Sports Med 2018 06 18;46(7):1596-1605. Epub 2018 Apr 18.

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.

Background: Partial anterior cruciate ligament (p-ACL) ruptures are a common injury of athletes. However, few preclinical models have investigated the natural history and treatment of p-ACL injuries.

Purpose: To (1) demonstrate whether a controlled p-ACL injury model (anteromedial band transection) develops progressive gross morphological and histological posttraumatic osteoarthritis (PTOA)-like changes at 20 and 40 weeks after the injury and (2) investigate the efficacy of repeated (0, 5, 10, and 15 weeks) intra-articular injections of methylprednisolone acetate (MPA; 80 mg/mL) in the mitigation of potential PTOA-like changes after p-ACL transection.

Study Design: Controlled laboratory study.

Methods: Twenty-one 3- to 5-year-old female Suffolk-cross sheep were allocated to 4 groups: (1) nonoperative controls (n = 5), (2) 20 weeks after p-ACL transection (n = 5), (3) 40 weeks after p-ACL transection (n = 6), and (4) 20 weeks after p-ACL transection + MPA (n = 5). Gross morphological grading and histological analyses were conducted. mRNA expression levels for inflammatory, degradative, and structural molecules were assessed.

Results: p-ACL transection led to significantly more combined gross damage ( P = .008) and significant aggregate histological damage ( P = .009) at 40 weeks after p-ACL transection than the nonoperative controls, and damage was progressive over time. Macroscopically, MPA appeared to slightly mitigate gross damage at 20 weeks after p-ACL transection in some animals. However, microscopic analysis revealed that repeated MPA injections after p-ACL transection led to significant loss in proteoglycan content compared with the nonoperative controls and 20 weeks after p-ACL transection ( P = .008 and P = .008, respectively).

Conclusion: p-ACL transection led to significant gross and histological damage by 40 weeks, which was progressive over time. Multiple repeated MPA injections were not appropriate to mitigate injury-related damage in a p-ACL transection ovine model as significant proteoglycan loss was observed in MPA-treated knees.

Clinical Relevance: A p-ACL injury leads to slow and progressive PTOA-like joint damage, and multiple repeated injections of glucocorticoids may be detrimental to the knee joint in the long term.
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http://dx.doi.org/10.1177/0363546518765098DOI Listing
June 2018

Scientific Overview on CSCI-CITAC Annual General Meeting and 2016 Young Investigators' Forum.

Clin Invest Med 2017 10 19;40(5):E211-E217. Epub 2017 Oct 19.

CITAC/ACCFC Executive Committee; MD/PhD Program, McGill University.

The 2016 Annual General Meeting of the Canadian Society of Clinician Investigators (CSCI) and Clinician Investigator Trainee Association of Canada/Association des Cliniciens-Chercheurs en Formation du Canada (CITAC/ACCFC) was a national conference held in Toronto November 21-23, 2016, in conjunction with The University of Toronto Clinician Investigator Program Research Day. The theme for this year's meeting was "Mapping Your Career as a Clinician-Scientist"; emphasizing essential skills for developing a fruitful career as clinician-scientist. The meeting featured an opening presentation by Dr. Alan Underhill, Dr. Nicola Jones and Alexandra Kuzyk. The keynote speakers were Dr. Nada Jabado (McGill University), who discussed the association between cancer and histones, Dr. Norman Rosenblum (University of Toronto), who addressed the career path and the "calling" of the Clinician Scientist, Dr. Martin Schmeing (McGill University), who was the 2016 Joe Doupe Award recipient, and Dr. Linda Rabeneck (Cancer Care Ontario and University of Toronto), who received the Friends of CIHR lectureship. The workshops, focusing on career development for clinician scientists, were hosted by Drs. Alan Underhill, Nicola Jones, Lynn Raymond, Michael Schlossmacher and Norman Rosenblum, as well as University of Toronto communication specialists, Caitlin Johannesson and Suzanne Gold. In addition, the Young Investigators' Forum included presentations from clinician investigator trainees from across the country. The research topics were diverse and comprehensive: from basic sciences to clinical practice; from epidemiology to medical engineering. All scientific abstracts are summarized in this review. Over 70 abstracts were showcased at this year's meeting during two poster sessions, with six outstanding abstracts selected for oral presentations during the President's Forum.
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http://dx.doi.org/10.25011/cim.v40i5.28626DOI Listing
October 2017

Location and gene-specific effects of methylprednisolone acetate on mitigating IL1β-induced inflammation in mature ovine explant knee tissue.

Inflamm Res 2017 Mar 16;66(3):239-248. Epub 2016 Nov 16.

McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Health Sciences Centre, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, T2N 4N1, Canada.

Objective And Design: To determine the ability of methylprednisolone acetate (MPA) to influence interleukin 1β (IL1β)-induced gene expression in ovine knee joint tissues.

Material Or Subjects: Ovine articular cartilage, synovium, and infrapatellar fat pad (IPFP) explants.

Treatment: Explants were treated with 10 M or 10 M MPA.

Methods: Explant treatment groups: (1) control (DMEM); (2) inflammation (IL1β); (3) IL1β + 10 M MPA; or (4) IL1β + 10 M MPA. Cell viability was assessed pre- and post-treatment. Expression of mRNA levels for inflammatory, degradative, anabolic, innate immunity, and adipose-related molecules was quantified via qPCR, and analyzed via the comparative C method.

Results: Except for IL8 in a subset of cartilage locations, matrix metalloproteinases (MMPs) were the only genes consistently affected by MPA. MPA mitigated IL1β-induced MMP3 expression levels in all regions of the articular cartilage, and in the synovium and IPFP, while MMP1 mRNA expression levels were significantly decreased with MPA after IL1β in the tibial plateau and synovium, but paradoxical increases in the IPFP. MMP13 mRNA expression levels exhibited significant decreases with MPA after IL1β in the femoral condyles, tibial plateau, synovium, and IPFP.

Conclusions: MPA treatment suppressed IL1β-induced mRNA levels for MMPs in articular cartilage, synovium, and IPFP and was found to be tissue-, location-, and gene-specific.
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http://dx.doi.org/10.1007/s00011-016-1009-zDOI Listing
March 2017

Use of pre-clinical surgically induced models to understand biomechanical and biological consequences of PTOA development.

J Orthop Res 2017 03 2;35(3):454-465. Epub 2017 Mar 2.

McCaig Institute for Bone & Joint Health, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

Post-traumatic osteoarthritis (PTOA) development is often observed following traumatic knee injuries involving key stabilising structures such as the cruciate ligaments or the menisci. Both biomechanical and biological alterations that follow knee injuries have been implicated in PTOA development, although it has not been possible to differentiate clearly between the two causal factors. This review critically examines the outcomes from pre-clinical lapine and ovine injury models arising in the authors' laboratories and differing in severity of PTOA development and progression. Specifically, we focus on how varying severity of knee injuries influence the subsequent alterations in kinematics, kinetics, and biological outcomes. The immediate impact of injury on the lubrication capacity of the joint is examined in the context of its influence on biomechanical alterations, thus linking the biological changes to abnormal kinematics, leading to a focus on the potential areas for interventions to inhibit or prevent development of the disease. We believe that PTOA results from altered cartilage surface interactions where biological and biomechanical factors intersect, and mitigating acute joint inflammation may be critical to prolonging PTOA development. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:454-465, 2017.
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http://dx.doi.org/10.1002/jor.23322DOI Listing
March 2017

Single intra-articular dexamethasone injection immediately post-surgery in a rabbit model mitigates early inflammatory responses and post-traumatic osteoarthritis-like alterations.

J Orthop Res 2015 Dec 7;33(12):1826-34. Epub 2015 Jul 7.

Department of Surgery, University of Calgary, McCaig Institute for Bone and Joint Health, Cumming School of Medicine, Calgary, Alberta, Canada.

Despite surgical reconstruction of the anterior cruciate ligament, a significant number of patients will still develop post-traumatic osteoarthritis (PTOA). Our objective was to determine if mitigating aspects of the acute phase of inflammation following a defined knee surgery with a single administration of a glucocorticoid could prevent the development of PTOA-like changes within an established rabbit model of surgically induced PTOA. An early and late post-surgical time-point was investigated in this study (48 h and 9 weeks post-surgery) in which the following groups were repeated (each n=6, for a total of 24 rabbits per time-point, and 48 rabbits used in the study): control (age/sex matched), sham (arthrotomy), drill injury (arthrotomy+two drill holes to a non-cartilaginous area of the femoral notch), and drill injury+single intra-articular (IA) injection of dexamethasone (DEX). At 48 h post-surgery, DEX treatment significantly lowered the mRNA levels for a subset of pro-inflammatory mediators, and significantly lowered the histological grade. Nine weeks post surgery, DEX treatment significantly lowered the histological scores (presented as effect size) for synovium (3.8), lateral femoral condyle (3.9), and lateral tibial cartilage (5.1) samples. Thus, DEX likely acts to prevent injury induced inflammation that could contribute to subsequent joint damage.
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http://dx.doi.org/10.1002/jor.22972DOI Listing
December 2015

Characterization of proteoglycan 4 and hyaluronan composition and lubrication function of ovine synovial fluid following knee surgery.

J Orthop Res 2013 Oct 30;31(10):1549-54. Epub 2013 May 30.

Faculty of Kinesiology, University of Calgary, Calgary, Alberta, Canada.

The objective of this study was to determine changes in (1) proteoglycan 4 (PRG4) and hyaluronan (HA) concentration, (2) HA molecular weight (MW) distribution, and (3) cartilage boundary lubricating ability of synovial fluid (SF) from surgical sham (SHAM), anterior cruciate ligament (ACL)/medial collateral ligament (MCL) transection, and lateral meniscectomy (MEN) in a post-knee surgery ovine model. Ovine SF (oSF) was collected at euthanization 20 weeks after surgery, with the contralateral joint serving as the non-operative control. PRG4 and HA concentration in oSF was measured by sandwich enzyme-linked immunosorbent assay, and HA MW distribution by agarose gel electrophoresis. Cartilage boundary lubricating ability of oSF was measured by a cartilage-cartilage friction test. PRG4 and HA concentration in SHAM, ACL/MCL, and MEN oSF were similar in comparison to the contralateral control (CTRL) oSF. The HA MW distribution in the operated oSF for all ranges were similar to the respective CTRL oSF. The kinetic coefficients of friction in operated and CTRL oSF were similar in all groups, and were significantly lower than saline. These results indicate oSF lubricant composition and function at 20 weeks post-knee surgery were similar to contralateral CTRL, and suggest earlier time points post surgery warrant further investigation.
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http://dx.doi.org/10.1002/jor.22399DOI Listing
October 2013
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