Migfilin’s elimination from osteoarthritic chondrocytes further promotes the osteoarthritic phenotype via β-catenin upregulation

Gkretsi, Vasiliki; Papanikolaou, Vassilis; Dubos, Stephanie; Papathanasiou, Ioanna V.; Giotopoulou, Nikolina; Valiakou, Vaia; Wu, Chuanyue; Malizos, Konstantinos N.; Tsezou, Aspasia

doi:10.1016/j.bbrc.2012.12.008

Cited by 7 publications

(7 citation statements)

References 36 publications

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“… 38 Accordingly, in examined osteoarthritis patient samples, both the mRNA and protein expression of Migfilin were dramatically elevated and correlated with the development and progression of disease. 39 The findings showing positive expression of Migfilin in human leiomyosarcoma and osteoarthritis have been supported by similar statistical analyses of other human malignancies. Increased Migfilin expression can be detected in advanced glioma tissue samples and indicates a poor patient outcome.…”

Section: Migfilin and Cancer Developmentsupporting

confidence: 55%

Migfilin: Cell Adhesion Effect and Comorbidities

Duan¹,

Qin

Gu³

et al. 2022

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Cell adhesion manifests as cell linkages to neighboring cells and/or the extracellular matrix (ECM). Migfilin is a widely expressed adhesion protein. It comprises three LIM domains in the C-terminal region and one proline-rich sequence in the N-terminal region. Through interplay with its various binding partners, such as Kindlin-2, Filamin, vasodilator-stimulated phosphoprotein (VASP) protein and the transcription factor CSX, Migfilin facilitates the dynamic association of connecting actomyosin fibers, orchestrating cell morphogenetic movement and cell adhesion, proliferation, migration, invasion, differentiation and signal transduction. In this review, to further elucidate the functional contributions of and pathogenesis induced by Migfilin, we focused on the structure of Migfilin and the targets which it directly binds with. We also summarized the role of Migfilin and its binding partners in the progression of different diseases and malignancies. As a possible candidate for coordinating various cellular processes and because of its association with both the pathogenesis and progression of certain tumors, Migfilin likely has utility as a therapeutic target against multiple diseases in the clinic.

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Section: Migfilin and Cancer Developmentsupporting

confidence: 55%

Migfilin: Cell Adhesion Effect and Comorbidities

Duan¹,

Qin

Gu³

et al. 2022

OTT

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“…We also found that CEMIP modulated the Wnt/β-catenin signaling, a well-known regulator of EMT, in human chondrocytes. The Wnt/β-catenin pathway contributes to OA pathogenesis 43,44 . We previously observed that β-catenin accumulated along chondrocytes dedifferentiation leading to leptin production 17 .…”

Section: Discussionmentioning

confidence: 99%

CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes

et al. 2019

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CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated β-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFβ signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into “chondro-myo-fibroblasts” expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these “chondro-myo-fibroblasts” were found in OA cartilage but not in healthy cartilage.

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“…The majority of these foci (61.5 %) were related to OA located within peripheral joints, spinal (zygapophyseal) joints and discs (discopathy) as shown by concomitant CT, which suggests involvement of integrin a v b 3 in OA. Structural changes in OA involve cartilage, fibrocartilaginous structures, synovium, subchondral bone and periarticular ligaments [36][37][38]. In response to mechanical or metabolic stress, the cartilage chondrocytes phenotype may change resembling to that of hypertrophic or dedifferentiated chondrocytes as obtained when primary chondrocytes are cultured in vitro, with a shift from anabolic to catabolic chondrocyte profile [38][39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%