Sulfasalazine Resolves Joint Stiffness in a Rabbit Model of Arthrofibrosis

Atluri, Keerthi; Brouillette, Marc J.; Seol, Dongrim; Khorsand, Behnoush; Sander, Edward A.; Salem, Aliasger K.; Fredericks, Douglas C.; Petersen, Emily; Smith, Sonja; Fowler, Timothy P.; Martin, James A.

doi:10.1002/jor.24499

Cited by 12 publications

(6 citation statements)

References 42 publications

(111 reference statements)

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“…To test first for an increase in functional contractility, we performed a gel compaction assay ( Fig. 2A) where we exposed fibroblast-populated fibrin gels to ACM or PCM for 48 hours, released the gel from the edges of the well, and measured the change in gel area 40,41 . All samples rapidly decreased in area post-release, with compaction in control and PCM samples proceeding for approximately seven hours before plateauing.…”

Section: Acm Increased Fibrin Gel Compaction and Fibroblast Contractimentioning

confidence: 99%

Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

El-Hattab

Nagumo

Gourronc

et al. 2020

Sci Rep

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Adipocytes and adipose tissue derived cells have been investigated for their potential to contribute to the wound healing process. However, the details of how these cells interact with other essential cell types, such as myofibroblasts/fibroblasts, remain unclear. Using a novel in-vitro 3D human adipocyte/ pre-adipocyte spheroid model, we investigated whether adipocytes and their precursors (preadipocytes) secrete factors that affect human dermal fibroblast behavior. We found that both adipocyte and pre-adipocyte conditioned medium induced the migration of fibroblasts, but only adipocyte conditioned medium induced fibroblast differentiation into a highly contractile, collagen producing myofibroblast phenotype. Furthermore, adipocyte mediated myofibroblast induction occurred through a tGf-β independent mechanism. Our findings contribute to a better understanding on the involvement of adipose tissue in wound healing, and may help to uncover and develop fat-related wound healing treatments.

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Section: Acm Increased Fibrin Gel Compaction and Fibroblast Contractimentioning

confidence: 99%

Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

El-Hattab

Nagumo

Gourronc

et al. 2020

Sci Rep

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“…ECM remodeling in the sclera can trigger fibroblast-to-myofibroblast differentiation 6 . Studies indicate that fibroblasts transform into myofibroblasts and upregulate α-SMA, which augments their ability to generate contractile force and increase ECM stiffness in myopic eyes 7 – 9 . Because the sclera undergoes remodeling throughout life, it is possible that the composition of scleral cell types and cell biology change during maturation and as sclera ages.…”

Section: Introductionmentioning

confidence: 99%

Scleral remodeling in early adulthood: the role of FGF-2

Qin,

Liu,

Zhang

et al. 2023

Sci Rep

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Emmetropization, a natural process of ocular elongation, is closely associated with scleral remodeling. The Fibroblast growth factor-2 (FGF-2) was reported involved in scleral remodeling in myopia models. Herein, we aimed to investigate the role of scleral fibroblast-to-myofibroblast differentiation and FGF-2 in scleral remodeling during maturation. Our findings revealed that the posterior scleral fibroblasts (SFs) from mature guinea pigs exhibit increased stiffness compared to those from young guinea pigs. Moreover, mature SFs displayed decreased cell proliferation but increased levels of α-SMA, matrix metalloproteinase 2 (MMP2), and collagen 1, when compared to young SFs. Additionally, the mRNA expression of scleral Fgf-2, Fgf receptor 1 (Fgfr1), Fgfr2, Fgfr3, and Fgfr4 was increased in mature SFs. Notably, exogenous FGF-2 showed increased cell proliferation and led to decreased expression of α-SMA, MMP2, and collagen 1 in mature SFs. Overall, our findings highlight the influence of maturation on SFs from posterior scleral shells, resulting in increased stiffness and the manifestation of fibroblast-to-myofibroblast differentiation during development. Exogenous FGF-2 increased cell proliferation and reversed the age-related fibroblast-to-myofibroblast differentiation, suggesting a potential role of FGF-2 in regulating scleral remodeling.

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“…[13][14][15] However, in vivo models of arthrofibrosis are costly, and the ability to control specific regulatory molecular pathways that contribute to the disease process is limited. To date, there are few in vitro options that are suitable to study myofibroblastogenesis, and these utilize fibroblasts derived from unknown sources, 16,17 cells from human tissues not associated with the local knee environment, 18 knee fibroblasts isolated from animals, 19 or primary cells isolated from the human knee environment with only partial phenotypic characterization. [20][21][22][23][24] Therefore, a well-characterized cell culture model for in vitro myofibroblastogenesis based on primary cultures of knee fibroblasts is essential for controlled experimentation to investigate arthrofibrotic processes at cellular, molecular, and biochemical levels.…”

Section: Introductionmentioning

confidence: 99%

Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation

Bayram

Thaler

Bettencourt

et al. 2022

J of Cellular Biochemistry

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Arthrofibrosis is characterized by excessive extracellular matrix (ECM) deposition that results in restricted joint motion after total knee arthroplasties (TKAs). Currently, treatment options are limited. Therefore, an in vitro model of knee-related myofibroblastogenesis is valuable to facilitate investigation of the arthrofibrotic process, diagnostic and therapeutic options. In this study, we obtained intraoperative posterior capsule (PC), quadriceps tendon (QT), and suprapatellar pouch (SP) tissues from the knees of four patients undergoing primary TKAs for osteoarthritis. From these tissues, we isolated primary cells by the outgrowth method and subsequently characterized these cells in the absence and presence of the pro-myofibroblastic cytokine, transforming growth factor beta 1 (TGFβ1). Light microscopy of knee outgrowth cells revealed spindle-shaped cells, and immunofluorescence (IF) analysis demonstrated staining for the fibroblast-specific markers TE-7 and vimentin (VIM). These knee outgrowth fibroblasts differentiated readily into myofibroblasts as reflected by enhanced α-smooth muscle actin (ACTA2) mRNA and protein expression and increased mRNA expression of collagen type 1 (COL1A1) and type 3 (COL3A1) with collagenous matrix deposition in the presence of TGFβ1.Outgrowth knee fibroblasts were more sensitive to TGFβ1-mediated myofibroblastogenesis than adipose-derived mesenchymal stromal/stem cells (MSCs). While outgrowth knee fibroblasts isolated from three anatomical regions in four patients exhibited similar gene expression, these cells are distinct from other fibroblastic cell types (i.e., Dupuytren's fibroblasts) as revealed by RNA-sequencing. In conclusion, our study provides an in vitro myofibroblastic model of outgrowth knee fibroblasts derived from patients undergoing

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Sulfasalazine Resolves Joint Stiffness in a Rabbit Model of Arthrofibrosis

Cited by 12 publications

References 42 publications

Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

Human Adipocyte Conditioned Medium Promotes In Vitro Fibroblast Conversion to Myofibroblasts

Scleral remodeling in early adulthood: the role of FGF-2

Human outgrowth knee fibroblasts from patients undergoing total knee arthroplasty exhibit a unique gene expression profile and undergo myofibroblastogenesis upon TGFβ1 stimulation

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