Deficiency of tenascin-C delays articular cartilage repair in mice

Okamura, Nobuyuki; Hasegawa, Masahiro; Nakoshi, Yutaka; Iino, Takahiro; Sudo, Akihiro; Imanaka‐Yoshida, Kyoko; Yoshida, Toshimichi; Uchida, Atsushi

doi:10.1016/j.joca.2009.08.013

Cited by 54 publications

(47 citation statements)

References 36 publications

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“…Treatment of human articular chondrocytes with TN-C was also shown to accelerate chondrocyte proliferation and play a role in cartilage repair [49]. These findings suggest involvement of TN-C in tissue remodeling that occurs in conjunction with degeneration and repair, which is further emphasized by the delay in articular cartilage repair observed for TN-C-deficient mice [53]. Indeed, we observed a pronounced increase in TN-C release into the joint fluid immediately after surgery in the rat model of OA/joint injury (Figure 8); TN-C levels decreased with time after surgery, indicating the transient expression of TN-C during the repair process.…”

Section: Discussionmentioning

confidence: 99%

Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

Patel

Sun

Glasson

et al. 2011

BMC Musculoskelet Disord

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BackgroundTenascin-C (TN-C) is an extracellular matrix glycoprotein that is involved in tissue injury and repair processes. We analyzed TN-C expression in normal and osteoarthritic (OA) human cartilage, and evaluated its capacity to induce inflammatory and catabolic mediators in chondrocytes in vitro. The effect of TN-C on proteoglycan loss from articular cartilage in culture was also assessed.MethodsTN-C in culture media, cartilage extracts, and synovial fluid of human and animal joints was quantified using a sandwich ELISA and/or analyzed by Western immunoblotting. mRNA expression of TN-C and aggrecanases were analyzed by Taqman assays. Human and bovine primary chondrocytes and/or explant culture systems were utilized to study TN-C induced inflammatory or catabolic mediators and proteoglycan loss. Total proteoglycan and aggrecanase -generated ARG-aggrecan fragments were quantified in human and rat synovial fluids by ELISA.ResultsTN-C protein and mRNA expression were significantly upregulated in OA cartilage with a concomitant elevation of TN-C levels in the synovial fluid of OA patients. IL-1 enhanced TN-C expression in articular cartilage. Addition of TN-C induced IL-6, PGE2, and nitrate release and upregulated ADAMTS4 mRNA in cultured primary human and bovine chondrocytes. TN-C treatment resulted in an increased loss of proteoglycan from cartilage explants in culture. A correlation was observed between TN-C and aggrecanase generated ARG-aggrecan fragment levels in the synovial fluid of human OA joints and in the lavage of rat joints that underwent surgical induction of OA.ConclusionsTN-C expression in the knee cartilage and TN-C levels measured in the synovial fluid are significantly enhanced in OA patients. Our findings suggest that the elevated levels of TN-C could induce inflammatory mediators and promote matrix degradation in OA joints.

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Section: Discussionmentioning

confidence: 99%

Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

Patel

Sun

Glasson

et al. 2011

BMC Musculoskelet Disord

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“…But in vivo studies in deficient mice (TnC-/-) have revealed a predominant role for TnC in supporting cartilage repair. TnC-/- mice develop cartilage erosion more rapidly after ACL and MCL transection, and cartilage repair is delayed in a focal cartilage defect model [111]. It is possible that the effect of TnC is modified by other factors present in vivo , but additional work is necessary to clarify.…”

Section: Methodsmentioning

confidence: 99%

Inflammation in joint injury and post-traumatic osteoarthritis

Lieberthal

Sambamurthy

Scanzello

2015

Osteoarthritis and Cartilage

374

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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“…88 However, tenascin-C knockout mice show very minor defects in wound healing exhibiting temporarily reduced fibronectin in the granulation tissue. 89 Impaired tissue repair was observed in these mice after corneal incision injury 90 and articular cartilage damage, 91 implying a possible role for tenascin-C in remodeling during repair. Tamaoki et al 92 showed in a model of myocardial injury that the tenascin-C FBG domain enhanced the migration of myocardial fibroblasts and promoted differentiation into myofibroblasts, in addition to increasing wound contraction.…”

Section: Patterns [Damps]mentioning

confidence: 97%

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

Zuliani-Alvarez

Midwood

2015

Advances in Wound Care

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Fibrinogen-related proteins (FRePs) comprise an intriguing collection of extracellular molecules, each containing a conserved fibrinogen-like globe (FBG). This group includes the eponymous fibrinogen as well as the tenascin, angiopoietin, and ficolin families. Many of these proteins are upregulated during tissue repair and exhibit diverse roles during wound healing. An increasing body of evidence highlights the specific expression of a number of FRePs following tissue injury and infection. Upon induction, each FReP uses its FBG domain to mediate quite distinct effects that contribute to different stages of tissue repair, such as driving coagulation, pathogen detection, inflammation, angiogenesis, and tissue remodeling. Despite a high degree of homology among FRePs, each contains unique sequences that enable their diversification of function. Comparative analysis of the structure and function of FRePs and precise mapping of regions that interact with a variety of ligands has started to reveal the underlying molecular mechanisms by which these proteins play very different roles using their common domain. Fibrinogen has long been used in the clinic as a synthetic matrix serving as a scaffold or a delivery system to aid tissue repair. Novel therapeutic strategies are now emerging that harness the use of other FRePs to improve wound healing outcomes. As we learn more about the underlying mechanisms by which each FReP contributes to the repair response, specific blockade, or indeed potentiation, of their function offers real potential to enable regulation of distinct processes during pathological wound healing.

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Deficiency of tenascin-C delays articular cartilage repair in mice

Abstract: This study revealed that cartilage repair in TNKO mice was significantly slower than that in WT mice and that the deficiency of TN-C progressed during cartilage degeneration.

Cited by 54 publications

References 36 publications

Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

Tenascin-C induces inflammatory mediators and matrix degradation in osteoarthritic cartilage

Inflammation in joint injury and post-traumatic osteoarthritis

Fibrinogen-Related Proteins in Tissue Repair: How a Unique Domain with a Common Structure Controls Diverse Aspects of Wound Healing

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