Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage

Wei, Tao; Kulkarni, Nalini H.; Zeng, Qing; Helvering, Leah M.; Lin, Xi; Lawrence, Frank R.; Hale, Laura V.; Chambers, M.G.; Lin, Chaohua; Harvey, A. McGehee; Ma, Yiming; Cain, R L; Oskins, J.L.; Carozza, M.A.; Edmondson, Denise; Hu, Tongzhou; Miles, Rebecca R.; Ryan, Timothy P.; Onyia, Jude E.; Mitchell, Peter G.

doi:10.1016/j.joca.2010.04.012

Cited by 72 publications

(73 citation statements)

References 29 publications

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“…Recent studies address how inflammatory gene expression varies with time after injury in common rodent models. Wei and colleagues [31] compared cartilage transcriptomic profiles in rats undergoing meniscal transection to sham-operated controls at days 3, 7 and 21 post-injury. 337 differentially expressed genes were observed at day 3, with smaller numbers at day 7 (79) and day 21 (112).…”

Section: Methodsmentioning

confidence: 99%

Inflammation in joint injury and post-traumatic osteoarthritis

Lieberthal

Sambamurthy

Scanzello

2015

Osteoarthritis and Cartilage

381

350

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Inflammation is a variable feature of osteoarthritis (OA), associated with joint symptoms and progression of disease. Signs of inflammation can be observed in joint fluids and tissues from patients with joint injuries at risk for development of post-traumatic osteoarthritis (PTOA). Furthermore, inflammatory mechanisms are hypothesized to contribute to the risk of OA development and progression after injury. Animal models of PTOA have been instrumental in understanding factors and mechanisms involved in chronic progressive cartilage degradation observed after a predisposing injury. Specific aspects of inflammation observed in humans, including cytokine and chemokine production, synovial reaction, cellular infiltration and inflammatory pathway activation, are also observed in models of PTOA. Many of these models are now being utilized to understand the impact of post-injury inflammatory response on PTOA development and progression, including risk of progressive cartilage degeneration and development of chronic symptoms post-injury. As evidenced from these models, a vigorous inflammatory response occurs very early after joint injury but is then sustained at a lower level at the later phases. This early inflammatory response contributes to the development of PTOA features including cartilage erosion and is potentially modifiable, but specific mediators may also play a role in tissue repair. Although the optimal approach and timing of anti-inflammatory interventions after joint injury are yet to be determined, this body of work should provide hope for the future of disease modification tin PTOA.

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Section: Methodsmentioning

confidence: 99%

Inflammation in joint injury and post-traumatic osteoarthritis

Lieberthal

Sambamurthy

Scanzello

2015

Osteoarthritis and Cartilage

381

350

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“…Many of these studies have focused on a single tissue, like articular cartilage 3, 4 , subchondral bone 5 or synovium 6, 7 most often at single time points. While these approaches have identified many novel genes with altered expression in OA, there is no information on how the gene product interactions may be altered to influence the development of the disease process.…”

Section: Introductionmentioning

confidence: 99%

Integration of gene expression data with network-based analysis to identify signaling and metabolic pathways regulated during the development of osteoarthritis

Olex

Turkett

Fetrow

et al. 2014

Gene

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Osteoarthritis (OA) is characterized by remodeling and degradation of joint tissues. Microarray studies have led to a better understanding of the molecular changes that occur in tissues affected by conditions such as OA; however, such analyses are limited to the identification of a list of genes with altered transcript expression, usually at a single time point during disease progression. While these lists have identified many novel genes that are altered during the disease process, they are unable to identify perturbed relationships between genes and gene products. In this work, we have integrated a time course gene expression data set with network analysis to gain a better systems level understanding of the early events that occur during the development of OA in a mouse model. The subnetworks that were enriched at one or more of the time points examined (2, 4, 8, and 16 weeks after induction of OA) contained genes from several pathways proposed to be important to the OA process, including the extracellular matrix-receptor interaction and the focal adhesion pathways and the Wnt, Hedgehog and TGF-β signaling pathways. The genes within the subnetworks were most active at the 2 and 4 week time points and included genes not previously studied in the OA process. A unique pathway, riboflavin metabolism, was active at the 4 week time point. These results suggest that the incorporation of network-type analyses along with time series microarray data will lead to advancements in our understanding of complex diseases such as OA at a systems level, and may provide novel insights into the pathways and processes involved in disease pathogenesis.

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“…Afterward, through the combination of good seed cell and gene engineering technology, the transfected cells were injected into the knee joint cavity. This strengthens target growth factor expression in cells, and the concentration reached a stable value [37]. And finally, the observation in cartilage repair effect was accomplished.…”

Section: Discussionmentioning

confidence: 77%

“…Also, in vivo experimental studies showed that TGF-β in chondrocytes mediates Smad2/3 signal through classical type I receptor ALK5, as well as Smad1/5/8 pathway through ALK1 receptor [35]. With the growth of age, the decrement of ALK5 was much faster as compared with ALK1, resulting in the differentiation of chondrocytes into the hypertrophic phenotype of osteoarthritis [36][37][38]. These studies might indicate that the decrease in ALK5/ALK1 ratio had broken the signal balance of TGF-β, so TGF-β signal was biased toward Smad1/5/8 signaling pathway, which made chondrocyte terminal differentiation and aggravated the process of cartilage arthritis.…”

Section: Discussionmentioning

confidence: 99%

ALK5 transfection of bone marrow mesenchymal stem cells to repair osteoarthritis of knee joint

Cao

Han

et al. 2018

Bio-des. Manuf.

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Previous studies have suggested that the transforming growth factor-β receptor ALK5 is crucial for articular chondrogenesis by bone marrow mesenchymal stem cells. Here, the wild-type ALK5 plasmids were mutated by overlapping extended PCR and transfected into bone marrow mesenchymal stem cells. The knee joint osteoarthritis mouse model was constructed by cutting off the anterior cruciate ligament and divided into three groups: saline group, bone marrow mesenchymal stem cells and ALK5-transfected bone marrow mesenchymal stem cells group. HE staining showed that the articular cartilage lesions were more serious of saline group compared with that of mesenchymal stem cell group, and this trend was more pronounced as time goes on. Immunohistochemical staining showed that although the expression level of type II collagen in all three groups down-regulated gradually upon time, its expression in ALK5-transfected bone marrow mesenchymal stem cells group was significantly enhanced compared with the other two groups. Micro-CT also suggested that ALK5 transfection of mouse bone marrow mesenchymal stem cells would promote repairing the knee cartilage lesions with arthritis of the mice. Although the osteoarthritis mechanism underlying a variety of factors work together, and the appropriate proportion of ALK5/ALK1 was also emphasized for the treatment of osteoarthritis. This work therefore demonstrated that ALK5 transfection of bone marrow mesenchymal stem cells could be a promising stem cell therapy for repair of cartilage lesions.

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Analysis of early changes in the articular cartilage transcriptisome in the rat meniscal tear model of osteoarthritis: pathway comparisons with the rat anterior cruciate transection model and with human osteoarthritic cartilage

Abstract: We identified a large number of differentially expressed genes in the articular cartilage of the MT model. While there was lack of overall identity in cartilage gene expression between the rat models and human OA, several key biological processes were recapitulated in the rat MT OA model.

Cited by 72 publications

References 29 publications

Inflammation in joint injury and post-traumatic osteoarthritis

Inflammation in joint injury and post-traumatic osteoarthritis

Integration of gene expression data with network-based analysis to identify signaling and metabolic pathways regulated during the development of osteoarthritis

ALK5 transfection of bone marrow mesenchymal stem cells to repair osteoarthritis of knee joint

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