Fibroblast growth factor 2: A new key player in osteoarthritis

Gavrilović, Jelena

doi:10.1002/art.24657

Cited by 7 publications

(6 citation statements)

References 24 publications

(26 reference statements)

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“…Numerous in vitro studies support the notion that low fluid shear (<10 dyn/cm 2 ) is chondroprotective, whereas high shear (>10 dyn/cm 2 ) promotes matrix degradation 19 . MMP-1 expression as well as superinduction of COX-2 accompanied by markedly increased levels of PGE 2 3 , 15d-PGJ 2 3 , IL-1β 10 and FGF-2 release 13 have been detected in OA-afflicted cartilage and in shear-activated human chondrocytes in vitro 3 . In view of the involvement of MMP-1 in matrix degrading signaling associated with OA disorders 15 16 17 18 and the role of fluid shear stress in the production of MMP-1 19 , we here delineated the signaling pathway of its induction in shear-stimulated human T/C-28a2 chondrocytes ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Treatment of human chondrocytes with exogenous IL-1β stimulates MMP expression in vitro 12 . Moreover, fibroblast growth factor-2 (FGF-2) was recently identified to be a new key player in OA 13 . FGF-2 is localized in a pericellular perlecan-bound pool in normal articular cartilage, but it is liberated from this pool in response to mechanical loading, which allows it to stimulate the ERK signaling pathway and the induction of certain MMPs 13 .…”

mentioning

confidence: 99%

“…Moreover, fibroblast growth factor-2 (FGF-2) was recently identified to be a new key player in OA 13 . FGF-2 is localized in a pericellular perlecan-bound pool in normal articular cartilage, but it is liberated from this pool in response to mechanical loading, which allows it to stimulate the ERK signaling pathway and the induction of certain MMPs 13 . In addition, Newberry et al 14 reported that the promoter of MMP-1 was activated by FGF-2 treatment in MC3T3-E1 osteoblasts.…”

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confidence: 99%

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The Role of Cyclooxygenase-2, Interleukin-1β and Fibroblast Growth Factor-2 in the Activation of Matrix Metalloproteinase-1 in Sheared-Chondrocytes and Articular Cartilage

Guan

Guo

et al. 2015

Sci Rep

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MMP-1 expression is detected in fluid shear stress (20 dyn/cm2)-activated and osteoarthritic human chondrocytes, however, the precise mechanisms underlying shear-induced MMP-1 synthesis remain unknown. Using primary chondrocytes and T/C-28a2 chondrocytic cells as model systems, we report that prolonged application of high fluid shear to human chondrocytes induced the synthesis of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β) and fibroblast growth factor-2 (FGF-2), which led to a marked increase in MMP-1 expression. IL-1β, COX-2-dependent PGE2 activated the PI3-K/AKT and p38 signaling pathways, which were in turn responsible for MMP-1 synthesis via NF-κB- and c-Jun-transactivating pathways. Prolonged shear stress exposure (>12 h) induced 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) synthesis. Although 15d-PGJ2 suppressed PI3-K/AKT and p38 signaling pathways, it stimulated MMP-1 expression via activating heme oxygenase 1 (HO-1). The critical role of COX-2 in regulating MMP-1 expression in articular cartilage in vivo was demonstrated using COX-2+/− transgenic mice in the absence or presence of rofecoxib oral administration. These findings provide novel insights for developing therapeutic strategies to combat OA.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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The Role of Cyclooxygenase-2, Interleukin-1β and Fibroblast Growth Factor-2 in the Activation of Matrix Metalloproteinase-1 in Sheared-Chondrocytes and Articular Cartilage

Guan

Guo

et al. 2015

Sci Rep

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“…FGF2 acts as a protective agent against aggressions 23 and is overexpressed in SF in animal knees subjected to mechanical overload or with chondral injuries. 24 For its part, TGFβ not only shares anabolic functions but also plays a part in apoptosis 25 and helps repair chondral and meniscal injuries. 26,27 In OA cartilage, it is overexpressed in the most superficial cells.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Gene Expression in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells in Osteoarthritis

Bravo

Argüello²,

Gortázar

et al. 2017

CARTILAGE

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Aim In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa's fat pad to differentiate into chondrocytes. Material and methodology We took knee Hoffa's pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction. Results PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFβ, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group. Conclusion OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.

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“…The release of perlecan-sequestered FGF-2 from the pericellular space of chondrocytes is thought to be important for its bioactivity (Jonca et al, 1997; Gavrilovic, 2009). To determine whether FGF-2 release is affected in the TIMP-deficient or Chloe/Jaffa crosses, we set up the femoral distal head explant culture system (Stanton et al, 2011) and used ELISA to measure FGF-2 in the supernatants.…”

Section: Resultsmentioning

confidence: 99%

Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth

Saw

Aiken

Fang

et al. 2019

Journal of Cell Biology

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Regulated growth plate activity is essential for postnatal bone development and body stature, yet the systems regulating epiphyseal fusion are poorly understood. Here, we show that the tissue inhibitors of metalloprotease (TIMP) gene family is essential for normal bone growth after birth. Whole-body quadruple-knockout mice lacking all four TIMPs have growth plate closure in long bones, precipitating limb shortening, epiphyseal distortion, and widespread chondrodysplasia. We identify TIMP/FGF-2/IHH as a novel nexus underlying bone lengthening where TIMPs negatively regulate the release of FGF-2 from chondrocytes to allow IHH expression. Using a knock-in approach that combines MMP-resistant or ADAMTS-resistant aggrecans with TIMP deficiency, we uncouple growth plate activity in axial and appendicular bones. Thus, natural metalloprotease inhibitors are crucial regulators of chondrocyte maturation program, growth plate integrity, and skeletal proportionality. Furthermore, individual and combinatorial TIMP-deficient mice demonstrate the redundancy of metalloprotease inhibitor function in embryonic and postnatal development.

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Fibroblast growth factor 2: A new key player in osteoarthritis

Cited by 7 publications

References 24 publications

The Role of Cyclooxygenase-2, Interleukin-1β and Fibroblast Growth Factor-2 in the Activation of Matrix Metalloproteinase-1 in Sheared-Chondrocytes and Articular Cartilage

The Role of Cyclooxygenase-2, Interleukin-1β and Fibroblast Growth Factor-2 in the Activation of Matrix Metalloproteinase-1 in Sheared-Chondrocytes and Articular Cartilage

Modulation of Gene Expression in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells in Osteoarthritis

Metalloprotease inhibitor TIMP proteins control FGF-2 bioavailability and regulate skeletal growth

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