Contrast enhanced μCT imaging of early articular changes in a pre-clinical model of osteoarthritis

Reece, David S; Thote, Tanushree; Lin, Angela; Willett, Nick J.; Guldberg, Robert E.

doi:10.1016/j.joca.2017.10.017

Cited by 23 publications

(30 citation statements)

References 35 publications

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“…However, significantly denser subchondral bone directly under the focal cartilage defects was detected in our model. This aligns with previous literature investigating instances of osteoarthritis in the knee of humans in which an increase in bone mineral density is considered an early sign of osteoarthritis . Combined with the presence of focal defects at 12 weeks, this model does appear to partially replicate the increased risk of developing osteoarthritis following rotator cuff tear seen in humans …”

Section: Discussionsupporting

confidence: 87%

Full‐thickness rotator cuff tear in rat results in distinct temporal expression of multiple proteases in tendon, muscle, and cartilage

Treviño

McFaline‐Figueroa

Guldberg

et al. 2018

Journal Orthopaedic Research

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The etiology of joint tissue degeneration following rotator cuff tear remains unclear. Thus, the purpose of this study was to understand the timeline of protease activity in the soft tissues of the shoulder (tendon, muscle, and cartilage) that may lead to downstream degeneration following rotator cuff tear. A well-established rat model involving suprascapular nerve denervation and supraspinatus/infraspinatus tendon transection was employed. Histological staining and/or micro-computed tomography (mCT) were used to observe structural damage in the supraspinatus tendon and muscle, humeral head cartilage, and subchondral bone. Multiplex gelatin zymography was utilized to assess protease activity in the supraspinatus tendon and muscle, and humeral head cartilage. Zymography analysis demonstrated that cathepsins were upregulated in the first week in all tissues, while MMP-2 maintained prolonged activity in supraspinatus tendon between 1 and 3 weeks and increased only at 3 weeks in supraspinatus muscle. In supraspinatus tendon, increased cathepsin L and MMP-2 activity in the first week was concurrent with matrix disorganization and infiltration of inflammatory cells. In contrast, significant upregulation of cathepsin L and K activity in supraspinatus muscle and humeral head cartilage did not correspond to any visible tissue damage at 1 week. However, focal defects developed in half of all animals' humeral head cartilage by 12 weeks (volume: 0.12 AE 0.09 mm 3 ). This work provides a more comprehensive understanding of biochemical changes to joint tissue over time following rotator cuff tear. Overall, this provides insight into potential therapeutic targets and will better inform ideal intervention times and treatments for each tissue. ß

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Section: Discussionsupporting

confidence: 87%

Full‐thickness rotator cuff tear in rat results in distinct temporal expression of multiple proteases in tendon, muscle, and cartilage

Treviño

McFaline‐Figueroa

Guldberg

et al. 2018

Journal Orthopaedic Research

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“…Articular cartilage surface roughness and exposed bone surface area (full thickness lesion surface area) were quantified using a custom MATLAB script, SurfaceRoughness function. 45 Briefly, coronal sections from the Scanco μ CT 40 were exported as 2D TIFF images and imported into MATLAB R2016a (MathWorks, Natick, MA, USA). A custom code created a 3D surface with these images by scanning section images sequentially and consolidating them.…”

Section: Surface Roughness Of Articular Cartilagementioning

confidence: 99%

“…the time point of the encapsulated hMSC intervention). 18,[43][44][45]55 While encapsulated hMSCs may not necessarily have any restorative properties that can reverse established disease damage, this treatment does have disease modifying potential that still provides high clinical translatability.…”

Section: Encapsulated Hmscs Attenuated Cartilage Degeneration In Estamentioning

confidence: 99%

Biomaterial encapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis

Ka²,

et al. 2020

Preprint

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Mesenchymal stromal cells (MSCs) have shown promise as a treatment for osteoarthritis (OA); however, effective translation has been limited by numerous factors ranging from high variability and heterogeneity of hMSCs, to suboptimal delivery strategies, to poor understanding of critical quality and potency attributes. The objective of the current study was to assess the effects of biomaterial encapsulation in alginate microcapsules on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA. Lewis rats underwent Medial Meniscal Transection (MMT) surgery to induce OA. Three weeks post-surgery, after OA was established, rats received intra-articular injections of either encapsulated hMSCs or controls (saline, empty capsules, or non-encapsulated hMSCs). Six weeks post-surgery, microstructural changes in the knee joint were quantified using contrast enhanced microCT. Encapsulated hMSCs attenuated progression of OA including articular cartilage degeneration (swelling and cartilage loss) and subchondral bone remodeling (thickening and hardening). A multiplexed immunoassay panel (41 cytokines) was used to profile the in vitro secretome of encapsulated and non-encapsulated hMSCs in response to IL-1□, a key cytokine involved in OA. Non-encapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1□ while encapsulated hMSCs showed a highly targeted secretory response with increased expression of some pro-inflammatory (IL-1β, IL-6, IL-7, IL-8), anti-inflammatory (IL-1RA), and chemotactic (G-CSF, MDC, IP10) cytokines. These data show that biomaterial encapsulation using alginate microcapsules can modulate hMSC paracrine signaling in response to OA cytokines and enhance the therapeutic efficacy of the hMSCs in treating established OA.

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“…Osteophytes are marginal tissue growths that form on the medial aspects of the tibial condyle and are a common symptom of OA 34 . Osteophyte volumes were evaluated using coronal sections generated by the scanning of the tibiae 35,36 . Cartilaginous osteophytes were isolated from surrounding air and bone using threshold values of 110-435 mg HA/cm 3 .…”

Section: Epic-μct Analysis Of Articular Cartilage Osteophytes and Sumentioning

confidence: 99%

“…To quantify surface roughness, coronal sections generated by scanning the tibiae were exported as 2D TIFF images and imported into MATLAB R2016a (MathWorks, Natick, MA). A custom code created a 3D surface with these images by scanning section images sequentially and fitting the 3D surface along a previously generated 3D polynomial surface: fourth order along the ventral-dorsal axis and second order along the medial-lateral axis 35 . The surface roughness was quantified as the root mean square of differences between the 3D surface created with the exported TIFF images and the polynomial fitted surface.…”

Section: Surface Roughness Analysis Of Articular Cartilagementioning

confidence: 99%

Characterization of OA development between sexes in the rat medial meniscal transection model

Pucha

McKinney

Fuller

et al. 2019

Preprint

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AbstractObjectiveOsteoarthritis (OA) is a chronic degenerative disease of the joints characterized by articular cartilage degradation. While there are clear sex differences in OA development in humans, most pre-clinical research has been conducted solely in male animals thus limiting the ability of these findings to be generalized to both sexes in the context of this disease. The objective of this study was to determine if sex impacts the progression and severity of OA in the rat medial meniscal tear (MMT) preclinical animal model used to surgically induce OA. It was hypothesized that differences would be observed between males and females following MMT surgery.DesignA MMT model was employed in male and female Lewis rats to induce OA. Animals were euthanized 3 weeks post-surgery and EPIC-μCT was used to quantitatively evaluate articular cartilage structure and composition, osteophyte volumes and subchondral bone structure.ResultsQuantitative analysis of the medial 1/3 articular cartilage via EPIC-μCT showed increased cartilage thickness and proteoglycan loss in the MMT of both sexes, when compared to sham. Additionally, both male and female animals in the MMT group had increased subchondral bone mineral density and larger total osteophyte volumes due to MMT.ConclusionThese data demonstrate that OA can be induced in both sexes using the rat MMT model. Moving forward, adding sex as a factor in preclinical OA studies should be standard practice in pre-clinical studies in order to elucidate more inclusive and translatable results into the clinic.

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Contrast enhanced μCT imaging of early articular changes in a pre-clinical model of osteoarthritis

Cited by 23 publications

References 35 publications

Full‐thickness rotator cuff tear in rat results in distinct temporal expression of multiple proteases in tendon, muscle, and cartilage

Full‐thickness rotator cuff tear in rat results in distinct temporal expression of multiple proteases in tendon, muscle, and cartilage

Biomaterial encapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis

Characterization of OA development between sexes in the rat medial meniscal transection model

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