Downregulation of dickkopf-1 enhances the proliferation and osteogenic potential of fibroblasts isolated from ankylosing spondylitis patients via the Wnt/β-catenin signaling pathway <i>in vitro</i>

Zou, Yong; Yang, Xian‐Wen; Yuan, Shiguo; Zhang, Pei; Ye, Yong-Liang; Li, Yikai

doi:10.3109/03008207.2015.1127916

Cited by 31 publications

(18 citation statements)

References 48 publications

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“…Increased growth rate and proliferation have been observed in AS fibroblasts (35), which is very similar to the results of the present study, indicating that ossification in AS is associated not only with fibroblast osteogenesis but also with proliferation compared with the controls. Therefore, the inhibition of proliferation of fibroblasts may be a potential strategy to prevent new bone formation in AS.…”

Section: Discussionsupporting

confidence: 91%

Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

Da-he

Gao

et al. 2019

Mol Med Report

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Ankylosing spondylitis (AS) is an autoimmune condition characterized by chronic inflammation and abnormal ossification as the primary features of the disease. The aim of the present study was to investigate the role of C-X-C chemokine receptor type 4 (CXCR4) in ossification from patients with AS. CXCR4 expression was assessed by western blot analysis and immunohistochemistry analysis of tissues obtained from patients with AS and controls. Fibroblasts were isolated, cultured and incubated with AMD 3100 and stromal cell-derived factor-1 to inhibit and promote CXCR4 levels, respectively. CXCR4 was upregulated in hip synovial tissues from patients with AS compared with that observed in controls. AS fibroblasts exhibited increased proliferation and growth rates. Inhibition of CXCR4 increased the phosphorylation of β-catenin and downregulated the expression of β-catenin, v-myc avian myelocytomatosis viral oncogene homolog, cyclin D1 and osteocalcin. Alizarin red staining demonstrated a decrease in biomineralization activity following the inhibition of CXCR4. These data support the hypothesis that inhibiting CXCR4 in patients with AS may suppress the ossification of fibroblasts.

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Section: Discussionsupporting

confidence: 91%

Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

Da-he

Gao

et al. 2019

Mol Med Report

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“…The formation of HO can be induced through both BMP/Smad pathway and BMP/P38 MAPK pathway [17][18][19]. In addition, signaling pathway including Hedgehog, Wnt-β-catenin and NF-κB also contribute to formation of HO [20][21][22]. In our case, a local hypoxic environment caused by the extensive hemangioma and vascular malformation is a possible mechanism for inducing ossification [23].…”

Section: Discussionmentioning

confidence: 62%

Diagnosis of Klippel-Trenaunay syndrome and extensive heterotopic ossification in a patient with a femoral fracture: a case report and literature review

Zhu

Xie

Yang

et al. 2020

BMC Musculoskelet Disord

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Background: Klippel-Trenaunay syndrome (KTS) is a rare complex vessel malformation syndrome characterized by venous varicosities, capillary malformations, and limb hypertrophy. However, extensive heterotopic ossification (HO) secondary to this syndrome is extremely rare. Case presentation: We report the case of a patient with previously undiagnosed KTS and extensive HO who presented with a femoral fracture secondary to a motor vehicle accident. Extensive ossification, which leads to compulsive contracture deformity and dysfunction of the leg, was distributed on the flexor muscle side, as revealed by the radiograph. The diagnosis was finally established by combining imaging and histological analysis with classical clinical symptoms. Amputation was performed at the fracture site proximal to the infected necrotic foci. Open management of the fracture was challenging owning to the pervasive ossification and tendency for excessive bleeding. Gene sequencing analysis showed homozygous mutation of FoxO1 gene. Conclusions: Definitive diagnosis of a combination of KTS and extensive HO requires detailed imaging analysis and pathologic evidence. Mutation of the FoxO1 gene, which regulates bone formation by resistance to oxidative stress in osteoblasts, is a potential factor in the microenvironment of malformed vessels caused by KTS.

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“…ANKH overexpression affects the Wnt/β-catenin signaling pathway in fibroblasts. The Wnt/β-catenin signaling pathway governs the differentiation of ossification and plays an important role in heterotopic ossification (25,31). The overexpression of ANKH significantly promoted β-catenin phosphorylation, whilst significantly downregulating the expression levels of β-catenin and c-Myc in AS fibroblasts compared with the control and NC groups (P<0.001; Fig.…”

Section: Ankh Expression Levels In Ligament Tissue From Patients Withmentioning

confidence: 91%

“…Thus, fibroblasts were suggested as likely contenders to be involved in osteogenesis (24). Fibroblasts and osteoblasts both originate from mesenchymal stem cell with overlapping phenotypes and through similar differentiation pathways, allowing fibroblasts to differentiate into osteoblasts and osteoblasts to differentiate into fibroblasts (25). In addition, the proliferative and osteogenic potential of fibroblasts was discovered to increase following the stimulation with fibronectin or BMP2 (26,27).…”

Section: Ankylosis Progressive Homolog Upregulation Inhibits Cell Viamentioning

confidence: 99%

Ankylosis progressive homolog upregulation inhibits cell viability and mineralization during fibroblast ossification by regulating the Wnt/β‑catenin signaling pathway

He¹,

Dong²

2020

Mol Med Rep

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ankylosis progressive homolog (anKH) is associated with fibroblast ossification in ankylosing spondylitis (AS). as the human anKH gene is poorly characterized relative to its murine counterpart, the aim of the present study was to examine anKH expression in ligament tissue isolated from patients with AS and the role played by this gene in AS-associated fibroblast ossification. Fibroblasts were isolated from ligament tissue collected from patients with aS and ligament tissue from individuals with spinal cord fractures, then cultured. Fibroblasts from patients with AS were subsequently transfected with an ANKH overexpression vector, while those collected from individuals with spinal cord fractures were transfected with small interfering rna specific for ANKH. Cell viability, apoptosis and mineralization were analyzed using MTT assays, flow cytometry and Alizarin Red staining, respectively. Furthermore, ANKH mrna and protein expression levels were analyzed using reverse transcription-quantitative PCR and western blotting analysis, respectively. The expression levels of osteogenesis markers, including alkaline phosphatase, osteocalcin, runt-related transcription factor 2, c-Myc, as well as the β-catenin signaling protein, were also determined using western blotting. The results of the present study revealed that anKH protein expression levels were downregulated in aS total ligament tissue extract, compared with spinal fracture ligament. Moreover, the fibroblasts derived from patients with AS exhibited an increased viability and reduced apoptosis rates, compared with the fibroblasts from patients with spinal fracture. Notably, ANKH overexpression inhibited viability, mineralization and ossification, increased the phosphorylation of β-catenin and downregulated β-catenin and c-Myc protein expression levels in fibroblasts from patients with AS. In addition, ANKH overexpression increased the ratio of p-β-catenin/β-catenin in fibroblasts from patients with AS. By contrast, ANKH silencing in fibroblasts from patients with spinal fracture resulted in the opposite effect. In conclusion, the findings of the present study suggested that ANKH may inhibit fibroblast viability, mineralization and ossification, possibly by regulating the Wnt/β-catenin signaling pathway.

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Downregulation of dickkopf-1 enhances the proliferation and osteogenic potential of fibroblasts isolated from ankylosing spondylitis patients via the Wnt/β-catenin signaling pathway in vitro

Abstract: AS fibroblasts are characterized by an imbalance between proliferation and apoptosis. DKK-1 may play a role in switching to new bone formation in AS progression.

Cited by 31 publications

References 48 publications

Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

Diagnosis of Klippel-Trenaunay syndrome and extensive heterotopic ossification in a patient with a femoral fracture: a case report and literature review

Ankylosis progressive homolog upregulation inhibits cell viability and mineralization during fibroblast ossification by regulating the Wnt/β‑catenin signaling pathway

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