Search bioRxiv⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/577866

Monosodium Iodoacetate delays regeneration and inhibits hypertrophy in skeletal muscle cells in vitro

Rimington, R. P.·Player, D. J.·Martin, N. R. W.·Lewis, M. P.
View original source ↗Export metadata ↓

Abstract

ObjectiveOsteoarthritis (OA) is a musculoskeletal disease which contributes to severe morbidity. The monosodium iodoacetate (MIA) rodent model of OA is now well established, however the effect of MIA on surrounding tissues post injection has not been investigated and as such the impact on phenotypic development is unknown. The aim of this investigation was to examine the impact of MIA incubation on skeletal muscle cells in vitro, to provide an indication as to the potential influence of MIA administration of skeletal muscle in vivo.\n\nMethodsC2C12 skeletal muscle myotubes were treated with either 4.8M MIA or 10M Dexamethasone (DEX, positive atrophic control) up to 72hrs post differentiation and sampled for morphological and mRNA analyses.\n\nResultsSignificant morphological effects (fusion index, number of myotubes and myotube width, p<0.05) were evident, demonstrating a hypertrophic phenotype in control (CON) compared to a hyperplasic phenotype in MIA and DEX. Increases in MAFbx mRNA were also evident between conditions, with post-hoc analysis demonstrating significance between CON and DEX (p<0.001), but not between CON and MIA (p>0.05).\n\nConclusionsThese data indicate a significant impact of both DEX and MIA on regeneration and hypertrophy in vitro and suggest differential activating mechanisms. Future investigations should determine whether skeletal muscle regeneration and hypertrophy is affected in the in vivo rodent model and the potential impact this has on the OA phenotypic outcome.

Explore related subjects

cell biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Rimington, R. P., Player, D. J., Martin, N. R. W., Lewis, M. P.. 2019-03-14. Monosodium Iodoacetate delays regeneration and inhibits hypertrophy in skeletal muscle cells in vitro. https://doi.org/10.1101/577866

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Sequential pathways preserve kinetochore integrity in meiosis

Kinetochores connect chromosomes to spindle microtubules, but how their integrity is maintained as they are remodelled during meiosis remains poorly understood. Here, we identify three distinct pathways linking centromeric chromatin to the outer kinetochore in budding yeast, mediated by the Ctf19 complex (Ctf19cCCAN), Mif2CENP-C and binding of Okp1CENP-Q-Ame1CENP-U to the Cse4CENP-A essential N-terminal domain (END). Although partially redundant during mitosis, all three connections are required during meiosis, with distinct temporal requirements. The assembled Ctf19cCCAN and Mif2CENP-C-dependent pathways maintain kinetochore integrity from meiotic entry, while Cse4CENP-A-Okp1CENP-Q-Ame1CENP-U binding becomes critical during prophase and the meiotic divisions. We further show that Ipl1Aurora B maintains kinetochore integrity independently of Ctf19cCCAN and provide evidence for an outer kinetochore-associated Ipl1Aurora B pool. Strikingly, Cse4CENP-A phosphomimetic mutations that restore kinetochore integrity upon Ipl1Aurora B depletion instead exacerbate defects in cells lacking Ctf19cCCAN. Our findings suggest that phosphorylation of the Cse4CENP-A N-terminal domain (NTD) by Ipl1Aurora B may regulate the use of alternative centromere-kinetochore connections to adapt to the changing requirements of meiosis.

cell biology↗
bioRxiv2026

Endothelial Cell Specific Thioredoxin 1-Dependent Signaling in Oxygen-1 Induced Retinopathy

Purpose: Retinopathy of prematurity (ROP) is a leading cause of childhood blindness, characterized byoxidative stress and dysregulated angiogenesis in preterm infants with immature antioxidant systems.This study aimed to investigate the specific role of endothelial cell-specific thioredoxin 1 (TXN1), a crucial oxidoreductase, in oxygen-induced retinopathy, hypothesizing that the absence of endothelial TXN1 directly impairs angiogenesis and exacerbates hyperoxia-induced injury. Methods: We generated tamoxifen-inducible, endothelial cell-specific Txn1 knockout mice (Txn1-iECKO) and utilized the oxygen-induced retinopathy (OIR) model, exposing litters to 85% oxygen from postnatal day 7 (P7) to P12. Retinal vascular morphology during vaso-obliteration and neovascularization phases, endothelial cell proliferation, and apoptotic cell death were assessed. Furthermore, human retinal microvascular endothelial cells (HRMECs) with TXN1 knockdown were subjected to hyperoxic conditions, followed by comprehensive gene expression profiling using RT2 Profiler PCR arrays and Ingenuity Pathway Analysis. Results: Deletion of endothelial Txn1 significantly enhanced vascular regression during the hyperoxic vaso-obliteration phase at P12 and markedly exacerbated pathological neovascularization at P17. Txn1-deficient retinas exhibited significantly impaired endothelial cell proliferation during the vaso-obliteration phase, while apoptotic cell death remained unchanged. Transcriptomic analysis of TXN1-deficient HRMECs under hyperoxia revealed an enhanced activation of NRF2-mediated oxidative stress response pathways. Conclusions: These findings identify endothelial TXN1 as an essential and oxygen-dependent regulator of vascular development in ischemic retinopathy, primarily influencing endothelial proliferation and redox signaling. This suggests TXN1's crucial protective role and highlights its therapeutic potential to mitigate ROP progression by modulating endothelial cell responses to oxidative stress.

cell biology↗
bioRxiv2026

A Dynamic Stem Cell State Links Environmental Cues to Skeletal and Regenerative Fates

Stem cells faithfully generate tissue architecture during development, yet how their identity and regenerative output are reshaped as anatomical niches mature and environmental signals change with aging and injury remains poorly understood. Rare skeletal stem cells (SSCs) across diverse skeletal sites are defined by combinations of cell-surface markers, precluding their genetic interrogation in vivo. Here, using spatially informed single cell transcriptomics, we identify Pannexin-3 (Panx3) to mark a dynamic functional state within bona fide SSCs and establish Panx3-CreERT2 mice for its longitudinal interrogation. Panx3 SSCs exhibit long-term clonal persistence, self-renewal and multipotency, whereas Panx3- SSCs can acquire this state. Successive SSC cohorts engage the Panx3 state during skeletal development, osteoanabolic stimulation expands pre-existing Panx3 SSC clones and injury induces it locally in previously unlabeled progenitors. Thus, anatomically distinct progenitors can converge on a common stem cell state in response to different environmental inputs. Three-dimensional reconstruction of chondrogenic niches further identifies signals that redirect Panx3-lineage cells towards stable cartilage, enabling durable regeneration in aged and osteoarthritic joints and with human SSCs. These findings establish anatomical origin, stem cell state and lineage fate as separable dimensions of stem cell identity and provide genetic access for interrogating and directing endogenous SSC function.

cell biology↗