Patterns of production of collagen‐rich deposits in peripheral nerves in response to injury: A pilot study in a rabbit model

Rivlin, Michael; Miller, A.; Tulipan, Jacob; Beredjiklian, Pedro K.; Wang, Mark L.; Fertala, Jolanta; Steplewski, Andrzej; Kostas, James; Fertala, Andrzej

doi:10.1002/brb3.659

Cited by 6 publications

(21 citation statements)

References 25 publications

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“…Although αSMA-positive myofibroblasts were not present in the stumps, we cannot exclude the possibility that they were present only transiently outside of our 2-to 10-week postinjury experimental time window. This possibility is in agreement with our study on the crush injury and partial-transection injury modes, where we observed some αSMA-positive fibroblasts 1-2 weeks after injury and with Chamberlain et al (2000), who observed αSMA-positive myofibroblasts only 60 days after injury (Rivlin et al, 2017).…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, the αSMA-positive staining was visible in the perineurial fibroblasts (data not shown) in which this marker is a natural intracellular component (Rivlin et al, 2017).…”

Section: Patterns Of Distribution Of Cells Expressing αSma and Hsp4mentioning

confidence: 84%

“…The specificity of staining of myelin with LFB is well documented, and this staining overlaps with immunostaining of myelin-specific proteins (Carriel, Garzon, Alaminos, & Campos, 2011;Kluver & Barrera, 1953;Rivlin et al, 2017;Xiang et al, 2005). Similarly, picrosirius red is a collagen-specific dye with high affinity to the triple-helical structure of fibrillar collagens (Junqueira, Bignolas, & Brentani, 1979).…”

Section: Histological Assaysmentioning

confidence: 93%

“…A microscope (Eclipse E600; Nikon, Inc.) was used to observe and photograph the nerve specimens. In addition, the samples stained only with picrosirius red were analyzed with a polarized light microscope (Eclipse LV100POL; Nikon Inc.), as described (Rivlin et al., 2017; Steplewski et al., 2016).…”

Section: Methodsmentioning

confidence: 99%

“…In particular, heat shock protein 47 (HSP47), a collagen‐specific protein chaperone that is upregulated during scar formation in a variety of human tissues, including injured joint capsules and nerves, plays a key role. Because of its close association with the collagen production, HSP47 serves as a reliable marker of collagen‐producing cells (Rivlin et al., 2017; Steplewski et al., 2016).…”

Section: Introductionmentioning

confidence: 99%

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Collagen‐rich deposit formation in the sciatic nerve after injury and surgical repair: A study of collagen‐producing cells in a rabbit model

et al. 2020

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Section: Discussionsupporting

confidence: 93%

“…Furthermore, the αSMA-positive staining was visible in the perineurial fibroblasts (data not shown) in which this marker is a natural intracellular component (Rivlin et al, 2017).…”

Section: Patterns Of Distribution Of Cells Expressing αSma and Hsp4mentioning

confidence: 84%

Section: Histological Assaysmentioning

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Collagen‐rich deposit formation in the sciatic nerve after injury and surgical repair: A study of collagen‐producing cells in a rabbit model

et al. 2020

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Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness

Hendy

Fertala

Nicholson

et al. 2023

Health Science Reports

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Background and Aims Arthrofibrosis is a severe scarring condition characterized by joint stiffness and pain. Fundamental to developing arthrofibrotic scars is the accelerated production of procollagen I, a precursor of collagen I molecules that form fibrotic deposits in affected joints. The procollagen I production mechanism comprises numerous elements, including enzymes, protein chaperones, and growth factors. This study aimed to elucidate the differences in the production of vital elements of this mechanism in surgical patients who developed significant posttraumatic arthrofibrosis and those who did not. Methods We studied a group of patients who underwent shoulder arthroscopic repair of the rotator cuff. Utilizing fibroblasts isolated from the patients' rotator intervals, we analyzed their responses to profibrotic stimulation with transforming growth factor β1 (TGFβ1). We compared TGFβ1‐dependent changes in the production of procollagen I. We studied auxiliary proteins, prolyl 4‐hydroxylase (P4H), and heat shock protein 47 (HSP47), that control procollagen stability and folding. A group of other proteins involved in excessive scar formation, including connective tissue growth factor (CTGF), α smooth muscle actin (αSMA), and fibronectin, was also analyzed. Results We observed robust TGFβ1‐dependent increases in the production of CTGF, HSP47, αSMA, procollagen I, and fibronectin in fibroblasts from both groups of patients. In contrast, TGFβ1‐dependent P4H production increased only in the stiff‐shoulder‐derived fibroblasts. Conclusion Results suggest P4H may serve as an element of a mechanism that modulates the fibrotic response after rotator cuff injury.

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Next-generation RNA sequencing elucidates transcriptomic signatures of pathophysiologic nerve regeneration

Warner

Stubben

Yeoh

et al. 2023

Sci Rep

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The cellular and molecular underpinnings of Wallerian degeneration have been robustly explored in laboratory models of successful nerve regeneration. In contrast, there is limited interrogation of failed regeneration, which is the challenge facing clinical practice. Specifically, we lack insight on the pathophysiologic mechanisms that lead to the formation of neuromas-in-continuity (NIC). To address this knowledge gap, we have developed and validated a novel basic science model of rapid-stretch nerve injury, which provides a biofidelic injury with NIC development and incomplete neurologic recovery. In this study, we applied next-generation RNA sequencing to elucidate the temporal transcriptional landscape of pathophysiologic nerve regeneration. To corroborate genetic analysis, nerves were subject to immunofluorescent staining for transcripts representative of the prominent biological pathways identified. Pathophysiologic nerve regeneration produces substantially altered genetic profiles both temporally and in the mature neuroma microenvironment, in contrast to the coordinated genetic signatures of Wallerian degeneration and successful regeneration. To our knowledge, this study presents as the first transcriptional study of NIC pathophysiology and has identified cellular death, fibrosis, neurodegeneration, metabolism, and unresolved inflammatory signatures that diverge from pathways elaborated by traditional models of successful nerve regeneration.

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Patterns of production of collagen‐rich deposits in peripheral nerves in response to injury: A pilot study in a rabbit model

Cited by 6 publications

References 25 publications

Collagen‐rich deposit formation in the sciatic nerve after injury and surgical repair: A study of collagen‐producing cells in a rabbit model

Collagen‐rich deposit formation in the sciatic nerve after injury and surgical repair: A study of collagen‐producing cells in a rabbit model

Profibrotic behavior of fibroblasts derived from patients that develop posttraumatic shoulder stiffness

Next-generation RNA sequencing elucidates transcriptomic signatures of pathophysiologic nerve regeneration

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