Follistatin‐like protein 1 (FSTL1) promotes chondrocyte expression of matrix metalloproteinase and inflammatory factors via the NF‐κB pathway

Hu, Pengfei; Ma, Chiyuan; Sun, Fangfang; Chen, Wei-Ping; Wu, Lidong

doi:10.1111/jcmm.14155

Cited by 20 publications

(13 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43 Besides, Hu et al declared that follistatin-like protein 1 elevated the levels of MMP-13, IL-1β, TNF-α and IL-6 by activating the NF-κB pathway in chondrocyte. 44 We found that Sal treatment markedly decreased the levels of MMP-13 and TNF-α. MMP-13 was an important regulator that maintained the metabolic balance of chondrocytes.…”

Section: Discussionmentioning

confidence: 66%

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Gao¹,

Lü

Li³

et al. 2020

DDDT

View full text Add to dashboard Cite

Introduction: Osteoarthritis (OA) is the most common disease, which seriously affects the daily life of the elderly. Currently, no traditional or drug therapy has been shown to explicitly block the progression of OA. Salidroside (Sal) is a bioactive component of Rhodiola rosea, which has many beneficial effects on human health. However, the role and mechanism of Sal in OA have not been reported. Methods: We established an anterior cruciate ligament transection (ACLT)-induced OA Rat model. The rats were divided into five groups (n = 10): Control group; ACLT group; ACLT + Sal (12.5 mg/kg) group; ACLT + Sal (25 mg/kg) group; ACLT + Sal (50 mg/kg) group. Results: The study showed that Sal could significantly promote the proliferation of chondrocytes in OA rats induced by ACLT and restore the histological alteration of cartilage. Besides, Sal upregulated the levels of Collagen II and Aggrecan, and downregulated the level of MMP-13. Furthermore, Sal could reduce the number of CD4+IL-17 + cells and decrease the levels of IL-17, IKBα and p65, while elevating the number of CD4+IL-10 + cells and the level of IL-10. The decrease of IL-17 further inhibited the dissociation of IKBα to p65, thus reducing the release of TNF-α and VCAM-1. Taken together, Sal alleviates cartilage degeneration through promoting chondrocytes proliferation, inhibiting collagen fibrosis, and regulating inflammation and immune responses via NF-κB pathway in ACLT-induced OA Rats. Discussion: Collectively, our study investigates the role and mechanism of Sal in OA, which lays a foundation for the application of Sal in OA.

show abstract

Section: Discussionmentioning

confidence: 66%

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Gao¹,

Lü

Li³

et al. 2020

DDDT

View full text Add to dashboard Cite

show abstract

“…Studies have shown that FSTL1 can alleviate the occurrence of inflammatory pulmonary fibrosis, suggesting that FSTL1 may be closely related to the occurrence of inflammation [23]. Further studies have reported that FSTL-1 regulates the secretion of inflammatory factors such as interleukin-α, TNF-α, and ADAMTS and participates in the immune inflammatory response in tissues in many systemic autoimmune diseases, including systemic lupus erythematosus, ulcerative colitis, rheumatoid arthritis, and Sjogren's syndrome [24,25]. In rheumatoid arthritis and osteoarthritis, FSTL1 exacerbates inflammation by increasing the expression of inflammatory factors and promoting synovial proliferation by activating the NF-κB signaling pathway [25].…”

Section: Introductionmentioning

confidence: 99%

Follistatin‐Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF‐α and Smad Signaling Pathway

Wang

Wei

Shi

et al. 2021

Oxidative Medicine and Cellular Longevity

View full text Add to dashboard Cite

Background. Inflammation plays an important role in intervertebral disc degeneration (IDD). The protein follistatin-like 1 (FSTL1) plays a proinflammatory role in a variety of inflammatory diseases. Objectives. The purpose of this study was to investigate whether IDD could be delayed by inhibiting FSTL-1 expression. Methods. We established a puncture-induced IDD model in wild-type and FSTL-1+/- mice and collected intervertebral discs (IVDs) from the mice. Safranin O staining was used to detect cartilage loss of IVD tissue, and HE staining was used to detect morphological changes of IVD tissue. We measured the expression of FSTL-1 and related inflammatory indicators in IVD tissues by immunohistochemical staining, real-time PCR, and Western blotting. Results. In the age-induced model of IDD, the level of FSTL-1 increased with the exacerbation of degeneration. In the puncture-induced IDD model, FSTL-1-knockdown mice showed a reduced degree of degeneration compared with that of wild-type mice. Further experiments showed that FSTL-1 knockdown also significantly reduced the level of related inflammatory factors in IVD. In vitro experiments showed that FSTL-1 knockdown significantly reduced TNF-α-induced inflammation. Specifically, the expression levels of the inflammatory factors COX-2, iNOS, MMP-13, and ADAMTS-5 were reduced. Knockdown of FSTL-1 attenuated inflammation by inhibiting the expression of P-Smad1/5/8, P-Erk1/2, and P-P65. Conclusion. Knockdown of FSTL-1 attenuated inflammation by inhibiting the TNF-α response and Smad pathway activity and ultimately delayed IDD.

show abstract

“…In a recently published study (50), FSTL1 increased the expression of inflammatory cytokines (IL‐1β, TNFα, IL‐6) and metalloproteinases, including MMP13, in rat chondrocytes. The results of this work are in contradiction with our data.…”

Section: Discussionmentioning

confidence: 87%

The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage

Chaly

Hostager

Smith

et al. 2020

ACR Open Rheumatology

View full text Add to dashboard Cite

Objective We sought to determine whether follistatin‐like protein 1 (FSTL1), a protein produced by articular chondrocytes, promotes healthy articular cartilage and prevents chondrocytes from undergoing terminal differentiation to hypertrophic cells. Methods In vitro experiments were performed with immortalized human articular chondrocytes. The cells were transduced with a lentivirus encoding human FSTL1 small hairpin RNA or with an adenovirus encoding FSTL1. A quantitative polymerase chain reaction was used for gene expression analysis. Protein expression was assessed by Western blotting. Co‐immunoprecipitation was used to identify interacting partners of FSTL1. FSTL1 expression in human articular cartilage was analyzed using confocal microscopy. Results Downregulation of FSTL1 expression in transforming growth factor β (TGFβ)‐stimulated chondrocyte pellet cultures led to chondrocyte terminal differentiation characterized by poor production of cartilage extracellular matrix and altered expression of genes and proteins involved in cartilage homeostasis, including MMP13, COL10A1, RUNX2, COL2A1, ACAN, Sox9, and phospho‐Smad3. We also showed that FSTL1 interacts with TGFβ receptor proteins, Alk1 and endoglin, suggesting a potential mechanism for its effects on chondrocytes. Transduction of chondrocytes with an FSTL1 transgene increased COL2A1 expression, whereas it did not affect MMP13 expression. FSTL1 protein expression was decreased in human osteoarthritic cartilage in situ. Conclusion Our data suggest that FSTL1 plays an important role in maintaining healthy articular cartilage and the FSTL1 pathway may represent a therapeutic target for degenerative diseases of cartilage.

show abstract

Follistatin‐like protein 1 (FSTL1) promotes chondrocyte expression of matrix metalloproteinase and inflammatory factors via the NF‐κB pathway

Cited by 20 publications

References 40 publications

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

<p>Salidroside Alleviates Cartilage Degeneration Through NF-κB Pathway in Osteoarthritis Rats</p>

Follistatin‐Like 1 Attenuation Suppresses Intervertebral Disc Degeneration in Mice through Interacting with TNF‐α and Smad Signaling Pathway

The Follistatin‐like Protein 1 Pathway Is Important for Maintaining Healthy Articular Cartilage

Contact Info

Product

Resources

About