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1. Fibroblast Growth Factor (FGF) 13

   https://doi.org/10.1016/j.diff.2024.100814  

   Rivas, Lucia J; Uribe, Rosa A (November 2024, Differentiation)
2. Synovial fibroblast gene expression is associated with sensory nerve growth and pain in rheumatoid arthritis

   https://doi.org/10.1126/scitranslmed.adk3506  

   Bai, Zilong; Bartelo, Nicholas; Aslam, Maryam; Murphy, Elisabeth A; Hale, Caryn R; Blachere, Nathalie E; Parveen, Salina; Spolaore, Edoardo; DiCarlo, Edward; Gravallese, Ellen M; et al (April 2024, Science Translational Medicine)

   It has been presumed that rheumatoid arthritis (RA) joint pain is related to inflammation in the synovium; however, recent studies reveal that pain scores in patients do not correlate with synovial inflammation. We developed a machine-learning approach (graph-based gene expression module identification or GbGMI) to identify an 815-gene expression module associated with pain in synovial biopsy samples from patients with established RA who had limited synovial inflammation at arthroplasty. We then validated this finding in an independent cohort of synovial biopsy samples from patients who had early untreated RA with little inflammation. Single-cell RNA sequencing analyses indicated that most of these 815 genes were most robustly expressed by lining layer synovial fibroblasts. Receptor-ligand interaction analysis predicted cross-talk between human lining layer fibroblasts and human dorsal root ganglion neurons expressing calcitonin gene–related peptide (CGRP⁺). Both RA synovial fibroblast culture supernatant and netrin-4, which is abundantly expressed by lining fibroblasts and was within the GbGMI-identified pain-associated gene module, increased the branching of pain-sensitive murine CGRP⁺dorsal root ganglion neurons in vitro. Imaging of solvent-cleared synovial tissue with little inflammation from humans with RA revealed CGRP⁺pain-sensing neurons encasing blood vessels growing into synovial hypertrophic papilla. Together, these findings support a model whereby synovial lining fibroblasts express genes associated with pain that enhance the growth of pain-sensing neurons into regions of synovial hypertrophy in RA. 

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3. Hydrogel mechanics regulate fibroblast DNA methylation and chromatin condensation

   https://doi.org/10.1039/D2BM02058K  

   Sumey, Jenna L.; Johnston, Peyton C.; Harrell, Abigail M.; Caliari, Steven R. (April 2023, Biomaterials Science)

   We engineered a hydrogel platform matching either normal or diseased lung tissue mechanics and tracked time-dependent changes in fibroblast DNA methylation and chromatin condensation in response to both static and dynamic mechanical cues. 

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4. DNA methylation dataset of bovine embryonic fibroblast cells treated with epigenetic modifiers and divergent energy supply

   https://doi.org/10.1016/j.dib.2022.108074  

   Diniz, Wellison J.S.; Crouse, Matthew S.; Caton, Joel S.; Claycombe-Larson, Kate J.; Lindholm-Perry, Amanda K.; Reynolds, Lawrence P.; Dahlen, Carl R.; Borowicz, Pawel P.; Ward, Alison K. (June 2022, Data in Brief)
5. Collagen I-Derived Extracellular Matrix Motifs Alter Fibroblast Regenerative Response

   https://doi.org/10.1159/000549101  

   Sanyaolu, Opemipo; Garza, Victoria; Santi, Athena; Romero_Uribe, Gabriela; Guda, Teja; Isaac, Alisa (October 2025, Cells Tissues Organs)

   Introduction: Damage-associated molecular patterns (DAMPs) are molecules released in response to tissue or cellular damage to facilitate tissue regeneration. This inflammatory response can occur in sterile environments and is promoted by the release of damaged extracellular components such as the extracellular matrix (ECM). DAMPs have been implicated in various stages of wound healing but have yet to be explicitly utilized for regenerative medicine by leveraging selective modulation of the inflammatory response. With this in mind, we leverage inflammation to drive tissue regeneration by utilizing DAMPs collected from the native ECM, extracellular matrix motifs (mECM). Methods: Here, mECMs were derived from UV-damaged rat tail collagen I. Fibroblast response to various concentrations and presentation of mECMs was investigated by evaluating changes in viability, proliferation, cell phenotype, and cytokine secretion. Results: mECMs had reduced intensity in collagen I associated bands, indicating successful fragmentation to lower molecular weights. Soluble (mobile) mECMs induced changes in fibroblast phenotype as indicated by a decrease in proliferation, a decrease in nuclei area, and an increase in the percentage of elongated cells. In addition, mobile mECMs contributed to significant increases in cytokine secretion compared to insoluble (bound) mECMs. Across all experiments, bound mECMs exhibited effects on fibroblasts compared to the collagen control. Conclusion: Fibroblasts in vitro recognize mECMs, with significant differences observed based on the presentation of these proteins. These data indicate that cryptic regions that are recognized by fibroblasts may be exposed in the mobile version of the mECMs, which lead to a myofibroblast-like phenotype in fibroblasts. This work highlights the potential of DAMPs to serve as immunomodulatory therapeutics for tissue regeneration. 

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