Citations

AimsTo evaluate the role of autophagy in primary knee fibroblasts undergoing myofibroblast differentiation as an in vitro model of arthrofibrosis, a complication after total knee arthroplasty characterized by aberrant intra-articular scar tissue formation and limited range of motion.MethodsWe conducted a therapeutic screen of autophagic-modulating therapies in primary human knee fibroblasts undergoing transforming growth factor-beta 1 (TGF-β1)-mediated myofibroblast differentiation. Autophagy was induced pharmacologically with rapamycin or by amino acid deprivation. Picrosirius red staining was performed to quantify collagen deposition. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were conducted to evaluate fibrotic gene expression levels.ResultsRapamycin, an mTOR complex 1 (mTORC1) inhibitor and autophagy inducer, reduced TGF-β1-mediated collagen deposition. Interestingly, we simultaneously report that myofibrogenic genes, including ACTA2, were highly upregulated following rapamycin-TGF-β1 treatment. When autophagy was induced through amino acid deprivation, we demonstrated suppressed extracellular matrix levels, fibrotic gene expression (e.g. ACTA2), and SMAD2 phosphorylation levels in TGF-β1-stimulated fibroblasts.ConclusionOur findings demonstrate that the induction of cellular autophagy suppresses TGF-β1-induced collagen deposition in primary human knee fibroblasts. Taken together, these data suggest that cellular autophagy may be prophylactic against the pathogenesis of arthrofibrosis.Cite this article: Bone Joint Res 2025;14(4):328–337.

Introduction Superficial parasternal intercostal plane blocks have grown in clinical use for cardiac surgery as a targeted fascial plane block for median sternotomy. Despite this, there remains no consensus on technique for optimal parasternal spread of injectate. The primary objective of this cadaveric study was to evaluate parasternal spread of injectate of single versus two-level superficial parasternal intercostal plane injections with the needle tip positioned on the anterior surface of the costal cartilage. Methods We performed 10 single-level injections at T4 and 10 two-level injections at T3 and T5 on alternating sides in 10 fresh frozen cadavers. All injections were ultrasound guided with a parasagittal ultrasound probe orientation and an in-plane needle orientation. Anatomic dissections were performed immediately following injections. Results Parasternal spread of injectate was greater with two-level injections at T3 and T5 costal cartilages than with single-level injections at the T4 costal cartilage, with two-level injections consistently spreading to the T2–T5 intercostal spaces. Median (Q1, Q3) intercostal space spread for single-level injections was 2.0 (2.0–2.5). Median (Q1, Q3) intercostal space spread for two-level injections was 4.0 (4.0–4.375). Conclusions Two-level injections with the needle tip located on the anterior surface of the costal cartilage resulted in improved parasternal spread compared with single-level injections.

Abstract Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.