Immobilization-Induced Cartilage Degeneration Mediated Through Expression of Hypoxia-Inducible Factor-1α, Vascular Endothelial Growth Factor, and Chondromodulin-I

Sakamoto, Juichi; Origuchi, Tomoki; Okita, Minoru; Nakano, Jun; Kato, Katsutomo; Yoshimura, Tsuyoshi; Izumi, Shinichi; Komori, Toshihisa; Nakamura, Hideki; Ida, Hiroaki; Kawakami, Atsushi; Eguchi, Katsumi

doi:10.1080/03008200802412454

Cited by 29 publications

(28 citation statements)

References 51 publications

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“…Furthermore, HIF-1α is essential for chondrogenesis, as it is associated with chondrocyte growth arrest, survival, maturation, and apoptosis (33–35). HIF-1α also regulates the configuration and maintenance of articular cartilage via the induction of anabolic factors and the suppression of key catabolic factors (36). The migration and invasion of fibroblast-like synoviocytes (FLSs) have also been demonstrated to be critical for the pathogenesis of OA (37,38).…”

Section: Discussionmentioning

confidence: 99%

Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

Qing

Lei

Liu

et al. 2016

Experimental and Therapeutic Medicine

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The aim of the present study was to examine hypoxia-inducible factor 1α (HIF-1α) levels in the synovial fluid and articular cartilage of patients with primary knee osteoarthritis (OA) and to investigate their association with the severity of disease. A total of 36 patients with knee OA and ten healthy controls were enrolled. Anteroposterior knee radiographs and/or Mankin scores were assessed to determine the disease severity of the affected knee. Radiographic grading of OA in the knee was performed according to Kellgren-Lawrence criteria. HIF-1α levels in synovial fluid were measured using enzyme-linked immunosorbent assay, whereas HIF-1α levels in articular cartilage were assessed with immunohistochemical methods. Compared with healthy controls, OA patients exhibited an increased HIF-1α concentration in synovial fluid (218.17±25.12 vs. 156.66±7.74 pg/ml; P<0.001) and articular cartilage (P<0.05). Furthermore, synovial fluid HIF-1α levels demonstrated a positive correlation with articular cartilage HIF-1α levels (Pearson's P=0.815; P<0.001). Subsequent analysis showed that synovial fluid HIF-1α levels were significantly correlated with the severity of disease (Spearman's ρ=0.933; P<0.001). Furthermore, articular cartilage levels of HIF-1α also correlated with disease severity (Spearman's ρ=−0.967; P<0.001). The findings of the present study suggested that HIF-1α in synovial fluid and articular cartilage is associated with progressive joint damage and is likely to be a useful biomarker for determining disease severity and progression in knee OA.

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Section: Discussionmentioning

confidence: 99%

Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

Qing

Lei

Liu

et al. 2016

Experimental and Therapeutic Medicine

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“…It is difficult to fully explain the discrepancy between increasing of the two growth factors and decreasing collagen type I mRNA from a fibrotic point of view, but hypoxia may remain as a possible cause. Immobilization of ankle joint with plaster casts induced hypoxia on the articular cartilage 40. Both TGF‐β1 and CTGF are induced by hypoxia, but their pathways by hypoxia are regulated independently 41…”

Section: Discussionmentioning

confidence: 99%

Expression patterns of collagen types I and III in the capsule of a rat knee contracture model

Hagiwara

Andõ

Onoda

et al. 2009

Journal Orthopaedic Research

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Our objective was to determine the changes in expression of collagen types I and III in the capsule of a rat knee contracture model. The unilateral knee joints of adult male rats were rigidly immobilized at 150 degrees of flexion using a rigid plastic plate and screws for 3 days, 1, 2, 4, 8, and 16 weeks (immobilized group). Sham-operated animals had holes drilled in the femur and tibia with screws inserted without a plate (control group). The expression patterns of collagen types I and III in the anterior and posterior capsule were evaluated by in situ hybridization (ISH), quantitative real-time polymerase chain reaction (qPCR), immunohistochemistry (IHC), and Western blotting (WB). Expressions of collagen types I and III were decreased after immobilization compared to the control group by ISH and qPCR. The expression was not changed after immobilization compared to the control group by IHC and WB. The expression of mRNA and protein levels of collagen types I and III were not increased after immobilization, which indicated that accumulation of the two types of collagen was not the etiology of joint contracture. Another process, such as capsule and synovial adhesions, may be one possible cause of joint contracture.

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“…However, we previously reported vascular invasions of the subchondral bone penetrating the cartilage 4 weeks after a spinal cord injury [22,23]. VEGF encourages vascular tissue formation from bone marrow into the articular cartilage [29,31]. Arguably, VEGF overexpression precedes neovascularization.…”

Section: Discussionmentioning

confidence: 99%

Amount of Torque and Duration of Stretching Affects Correction of Knee Contracture in a Rat Model of Spinal Cord Injury

Moriyama¹,

Tobimatsu²,

Ozawa³

et al. 2013

Clinical Orthopaedics &Amp; Related Research

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Background Joint contractures are a common complication of many neurologic conditions, and stretching often is advocated to prevent and treat these contractures. However, the magnitude and duration of the stretching done in practice usually are guided by subjective clinical impressions. Questions/purposes Using an established T8 spinal cord injury rat model of knee contracture, we sought to determine what combination of static or intermittent stretching, varied by magnitude (high or low) and duration (long or short), leads to the best (1) improvement in the limitation in ROM; (2) restoration of the muscular and articular factors leading to contractures; and (3) prevention and treatment of contracture-associated histologic alterations of joint capsule and articular cartilage. Methods Using a rat animal model, the spinal cord was transected completely at the level of T8. The rats were randomly assigned to seven treatment groups (n = 4 per group), which were composed of static or intermittent stretching in combination with different amounts of applied torque magnitude and duration. We assessed the effect of stretching by measuring the ROM and evaluating the histologic alteration of the capsule and cartilage. Results Contractures improved in all treated groups except for the low-torque and short-duration static stretching conditions. High-torque stretching was effective against shortening of the synovial membrane and adhesions in the posterosuperior regions. Collagen Type II and VEGF in the cartilage were increased by stretching. Conclusions High-torque and long-duration static stretching led to greater restoration of ROM than the other torque and duration treatment groups. Stretching was more effective in improving articular components of contractures compared with the muscular components. Stretching in this rat model prevented shortening and adhesion of the joint capsule, and affected biochemical composition, but did not change morphologic features of the cartilage. Clinical Relevance This animal study tends to support the ideas that static stretching can influence joint ROM and histologic qualities of joint tissues, and that the way stretching is performed influences its efficacy. However, further studies are warranted to determine if our findings are clinically applicable.

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Immobilization-Induced Cartilage Degeneration Mediated Through Expression of Hypoxia-Inducible Factor-1α, Vascular Endothelial Growth Factor, and Chondromodulin-I

Cited by 29 publications

References 51 publications

Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

Expression of hypoxia-inducible factor-1α in synovial fluid and articular cartilage is associated with disease severity in knee osteoarthritis

Expression patterns of collagen types I and III in the capsule of a rat knee contracture model

Amount of Torque and Duration of Stretching Affects Correction of Knee Contracture in a Rat Model of Spinal Cord Injury

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