Animal models for osteoarthritis: processes, problems and prospects.

Pritzker, Kenneth P.H.

doi:10.1136/ard.53.6.406

Cited by 123 publications

(80 citation statements)

References 130 publications

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“…5D4. 3B3(-), and 3B3(+) were assayed by ELISA according to previously published methods (14, 85,104,108), with exceptions to bc dcscribed. All samples and standards were assaycd in duplicate at a minimum.…”

Section: Enzymc-linked Lmmunosorbent Assay (Elisa)mentioning

confidence: 99%

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis

Lindhorst

Vail

Guilak

et al. 2000

Journal Orthopaedic Research

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Summary: Damage to the meniscus can lead to posttraumatic osteoarthritis. Early markers of joint injury and tissue disease may be useful in developing and administering clinical treatmenl. We investigated the effects of total medial meniscectomy on biomarkers measurcd serially in synovial lavage fluid each month for 3 months. Following meniscectomy in dogs, four biomarkers were evaluated: cartilage oligomeric matrix protein, keratan sulfate epitope (5D4). the 3R3(-) neoepitope of chondroitin-(,-sulfate, and the 3B3(+) chondroitinasegenerated epitope of chondroitin-6-sulfate. Meniscectomy led to statistically significant elevations of all four biomarkers, with levels peaking at 4 weeks. By 12 weeks. the level of thc SD4 epitopc returned to the prcoperative baseline level whereas that of cartilage oligomeric matrix protein. 3B3(-), and 3B3(+) remained above the baseline. Concentrations of these biomarkers in the knees not operated on did not change significantly from the baseline. The levels of cartilage oligomeric matrix protein and 3B3(-) relativc to 3B3(+) rcrnained constant in all knees. In contrast. the level of SD4 relativc to 3B3(+) declined over time in the knee operated on but remained constant in the knee not operated on. These results demonstrate a quantitative change in the molecular componenls of synovial fluid after meniscectomy. as well as a qualitative change evinced by an alteration in the relative proportions of these epitopes. Extensive analyses showed a strong correlation between serum levcls of 3B3( -) from thc femorai and cephalic veins; however, serum 3B3(-) was not correlated with synovial h i d 3B3( -). These findings support the hypothesis that the conccntrations of select cartilage biomarkers in synovial fluid are altered following meniscectomy and are promising tools for objectively monitoring the induction of osteoarthritis in this model system.The menisci have been shown to be critical for normal function and health of the knee joint (42,78), serving crucial roles in load transmission (3), shock absorption (86), joint congruence (59) and stability (63), and likely proprioception (26,31,80,112). Meniscal injury is quite common (12), second in frequency only to ligamentous strain (9,32,48,56,93). It is the most common injury sustained by athletes (100) and i s the predominant injury associated with chondral damage beyond the third decade of life (29). Observations of the natural history of meniscal damage reveal deleterious long-term consequences. As many as 20-60% of patients with an isolated injury of the meniscus had radiographic signs of joint degeneration (32.94). Knee injury may occur at an early age, with the first radiographic signs of osteoarthritis ensuing, on average,

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Section: Enzymc-linked Lmmunosorbent Assay (Elisa)mentioning

confidence: 99%

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis

Lindhorst

Vail

Guilak

et al. 2000

Journal Orthopaedic Research

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“…Rodent models that have been used for the study of pain in OA include monosodium iodoacetate, collagenase, or papain injection into the knee joint, or partial meniscectomy (6,7). These models characteristically produce severe and rapidly progressive joint damage, with behavioral changes occurring within days of the procedure.…”

mentioning

confidence: 99%

Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system

Inglis

McNamee

Chia

et al. 2008

Arthritis & Rheumatism

106

126

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Objective. OA is the most common joint disease, affecting 10-15% of people over 60 years of age. However, up to 40% of individuals with radiologic damage are asymptomatic. The purpose of this study was to assess the role of the endogenous opioid system in delaying the onset of pain in a murine model of osteoarthritis (OA).Methods. Osteoarthritis was induced by transection of the medial meniscotibial ligament. Pain was assessed by monitoring weight distribution and activity. At various times postsurgery, the opioid receptor antagonists naloxone or peripherally restricted naloxone methiodide were administered, and pain was assessed. Levels of the -opioid receptor were assessed in the nerves innervating the joint by real-time reverse transcription-polymerase chain reaction analysis.Results. As in human disease, significant joint damage occurred in mice before the onset of pain. To assess whether delayed pain was partly the result of increased endogenous opioid function, naloxone or naloxone methiodide was administered. Both opioid receptor antagonists led to pain onset 4 weeks earlier than in vehicle-treated mice, indicating a role of the peripheral opioid system in masking OA pain. The expression of the -opioid receptor in the peripheral nerves supplying the joint was transiently increased in naloxoneresponsive mice. Conclusion.These findings indicate that a temporal induction of -opioid receptors in the early stages of OA delays the onset of pain. This is of clinical relevance and may contribute to the assessment of patients presenting with pain late in the disease. Furthermore, it may point to a mechanism by which the body blocks pain perception in moderate states of tissue damage, allowing an increased chance of survival.

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“…In this study, anatomical 3D scaffolds for meniscal replacement have been fabricated with matching natural menisci biomechanical properties and their beneficial use numerically evaluated in terms of articular cartilage damage. Scaffolds were modelled from CT or MRI datasets of a porcine meniscus, which was chosen as a testing model because of its similarity with humans [28,29,41]. From a processing point of view, CT datasets were found to be more accurate and precise than MRI.…”

Section: Discussionmentioning

confidence: 99%

“…The Open Biomedical Engineering Journal, 2007, Volume 1 29 mately 30% higher while the maximal shear strain was about 10% higher than in healthy conditions.…”

Section: Finite Element Analysis Of Meniscal Anatomical 3d Scaffoldsmentioning

confidence: 99%

“…A porcine meniscal model was considered, since its dimensions and loading are comparable to human menisci [28,29]. The anatomical 3D scaffolds were experimentally analyzed to tailor their mechanical properties to match those of natural menisci and numerically investigated with finite element analysis (FEA) to determine whether such a construct is -at least from a biomechanical point of view -beneficial for meniscus reconstruction as compared to meniscectomy.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Finite Element Analysis of Meniscal Anatomical 3D Scaffolds: Implications for Tissue Engineering

Moroni¹,

Lambers²,

Wilson³

et al. 2007

TOBEJ

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Solid Free-Form Fabrication (SFF) technologies allow the fabrication of anatomical 3D scaffolds from computer tomography (CT) or magnetic resonance imaging (MRI) patients' dataset. These structures can be designed and fabricated with a variable, interconnected and accessible porous network, resulting in modulable mechanical properties, permeability, and architecture that can be tailored to mimic a specific tissue to replace or regenerate. In this study, we evaluated whether anatomical meniscal 3D scaffolds with matching mechanical properties and architecture are beneficial for meniscus replacement as compared to meniscectomy. After acquiring CT and MRI of porcine menisci, 3D fiber-deposited (3DF) scaffolds were fabricated with different architectures by varying the deposition pattern of the fibers comprising the final structure. The mechanical behaviour of 3DF scaffolds with different architectures and of porcine menisci was measured by static and dynamic mechanical analysis and the effect of these tissue engineering templates on articular cartilage was assessed by finite element analysis (FEA) and compared to healthy conditions or to meniscectomy. Results show that 3DF anatomical menisci scaffolds can be fabricated with pore different architectures and with mechanical properties matching those of natural menisci. FEA predicted a beneficial effect of meniscus replacement with 3D scaffolds in different mechanical loading conditions as compared to meniscectomy. No influence of the internal scaffold architecture was found on articular cartilage damage. Although FEA predictions should be further confirmed by in vitro and in vivo experiments, this study highlights meniscus replacement by SFF anatomical scaffolds as a potential alternative to meniscectomy.

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Animal models for osteoarthritis: processes, problems and prospects.

Cited by 123 publications

References 130 publications

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis

Longitudinal characterization of synovial fluid biomarkers in the canine meniscectomy model of osteoarthritis

Regulation of pain sensitivity in experimental osteoarthritis by the endogenous peripheral opioid system

Finite Element Analysis of Meniscal Anatomical 3D Scaffolds: Implications for Tissue Engineering

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