Osteoarthritis development in novel experimental mouse models induced by knee joint instability

Kamekura, Satoru; Hoshi, Kazuto; Shimoaka, Takashi; Chung, Ung‐il; Chikuda, Hirotaka; Yamada, Takashi; Uchida, Motoyuki; Ogata, Naoshi; Seichi, Atsushi; Nakamura, Kozo; Kawaguchi, Hiroshi

doi:10.1016/j.joca.2005.03.004

Cited by 500 publications

(550 citation statements)

References 37 publications

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“…Kamekura et al showed that MMP-13 expression was induced in instability-induced OA cartilage, and that MMP-13 was colocalized with type X collagen in hypertrophic chondrocytes (7). Those authors suggested that up-regulated expression of MMP-13 in abnormal hypertrophic chondrocytes plays a key role in cartilage degradation.…”

Section: Discussionmentioning

confidence: 99%

“…The main causes of OA are considered to be aging and excessive mechanical stress to the joints, due to joint instability or obesity (2). A number of in vivo studies using various joint instability models have clarified some aspects of the molecular mechanisms comprising the response to excessive mechanical stress to the joints (3)(4)(5)(6)(7)(8). However, the mechanisms of agingassociated development of OA have not been clearly elucidated.…”

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confidence: 99%

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Accelerated development of aging‐associated and instability‐induced osteoarthritis in osteopontin‐deficient mice

Matsui¹,

Iwasaki²,

Kawa³

et al. 2009

Arthritis & Rheumatism

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Objective. To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions.Methods. Both instability-induced and agingassociated OA models were generated using OPNdeficient (OPN ؊/؊ ) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage.Results. OPN deficiency exacerbated both agingassociated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen-degrading enzyme MMP-13 facilitated the development of OA.Conclusion. OPN plays a pivotal role in the progression of both instability-induced and agingassociated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Accelerated development of aging‐associated and instability‐induced osteoarthritis in osteopontin‐deficient mice

Matsui¹,

Iwasaki²,

Kawa³

et al. 2009

Arthritis & Rheumatism

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“…In a severe mouse osteoarthritis model in which the anterior and posterior cruciate ligaments, the medial and lateral collateral ligaments, and the medial and lateral menisci were removed, all the mice developed osteophytes through endochondral ossification 8 weeks post-surgery. 21 Other methods, such as ACLT-induced osteoarthritis combined with menisci removal, may provide a more proper model for evaluating the effect of TSP-1 on endochondral ossification in rats.…”

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confidence: 99%

Intraarticular gene transfer of thrombospondin‐1 suppresses the disease progression of experimental osteoarthritis

Hsieh

Shen

Shiau

et al. 2010

Journal Orthopaedic Research

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In osteoarthritis, angiogenesis, which occurs in the osteochondral junction and synovium, may accelerate inflammation and contribute to the severity of the disease. We used anterior cruciate ligament-transection (ACLT) to investigate the therapeutic effect of an angiogenesis inhibitor, thrombospondin-1 (TSP-1), in a rat model of osteoarthritis. Osteoarthritis was induced in Wistar rats in the knee of one hind leg. After ACLT, AdTSP-1 (adenoviral vector encoding mouse TSP-1) was intraarticularly injected into the knee joints. Transgene expression, angiogenesis, and inflammatory responses in the knee joints were examined. They were also assessed morphologically, radiographically, and histologically for manifestations of disease. The levels of TSP-1 peaked on day 3 and were substantially maintained for at least 9 days after AdTSP-1 infection. Adenovirus-mediated gene expression was detected in the synovial membrane and chondrocytes. TSP-1 gene transfer induced transforming growth factor-b (TGF-b) production, but it reduced microvessel density, macrophage infiltration, and interleukin-1b (IL-1b) levels. Gross morphological and histopathological examinations revealed that rats treated with AdTSP-1 had less severe osteoarthritis than controls. In vivo adenovirus-mediated TSP-1 gene transfer significantly reduced microvessel density, inflammation, and suppressed the progression of osteoarthritis. This study provides potential applications of TSP-1 gene delivery for treating osteoarthritis. ß

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“…However, these changes were superficial and showed early osteoarthritis stages due to the collagenase concentration, according to Kikuchi et al 6 . The ACLT method has created degenerative cartilage lesions after 12 weeks, as well as more severe degradation 4,15,16 .…”

Section: Discussionmentioning

confidence: 99%

“…These models were designed using different mechanisms through which stress leads to OA development, namely: the transection of the meniscus and/or ligaments 4 , the intra-articular injection of a chemical substance such as papain 5 or collagenase 6 . The knee dynamics stability is affected by both the passive (ligamentous) and active (neuromuscular) joint restraints.…”

Section: Introductionmentioning

confidence: 99%

Comparison between two different experimental models of osteoarthritis in rabbits. Intra-articular collagenase injection and anterior cruciate ligament transection

Hermeto

Rossi²,

Jardim³

et al. 2016

Acta Cir. Bras.

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PURPOSE:To compare two different experimental models of osteoarthritis in rabbits: intra-articular collagenase injection and anterior cruciate ligament transection. METHODS:Ten adult rabbits were randomly divided in two groups: COLL (collagenase group) and ACLT (anterior cruciate ligament transection). The COLL group was treated with 0.5 ml collagenase solution (2mg collagenase/0.5 ml sterile PBS), and the ACTL group was subjected to anterior cruciate ligament. After six and twelve weeks, respectively, the animals in the COLL and ACTL groups were euthanized. The gross appearance and histological examinations conducted in the cartilage articular surface was blindly scored according to the criteria developed by Yoshimi et al. (1994) and Mankin et al. (1971), respectively. RESULTS:The gross morphologic observation, macroscopic score and histological examinations have demonstrated that the ACTL group presented the highest scores, and lesions more severe than those in the COLL group. CONCLUSIONS: Both methods, anterior cruciate ligament transection and collagenase, applied to the stifle joint of the rabbits have effectively induced degenerative changes in the cartilage tissue, through statistically significant analysis (p≤0.05). The ACTL method has presented more severe lesions.

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Osteoarthritis development in novel experimental mouse models induced by knee joint instability

Abstract: We established four types of mouse models exhibiting various speeds of OA progression. By applying a mouse genomics approach to the models, molecular backgrounds in various stages of OA development can be clarified.

Cited by 500 publications

References 37 publications

Accelerated development of aging‐associated and instability‐induced osteoarthritis in osteopontin‐deficient mice

Accelerated development of aging‐associated and instability‐induced osteoarthritis in osteopontin‐deficient mice

Intraarticular gene transfer of thrombospondin‐1 suppresses the disease progression of experimental osteoarthritis

Comparison between two different experimental models of osteoarthritis in rabbits. Intra-articular collagenase injection and anterior cruciate ligament transection

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