Effects of ECM Components on Periodontal Ligament Stem Cell Differentiation Under Conditions of Disruption of Wnt and TGF-β Signaling PathwaysKuznetsova, Popova, Danilova
et alJ Funct Biomater (2025) 16 (3)
Abstract: Periodontitis is accompanied by inflammation that causes dysregulation of the Wnt/β-catenin and TGF-β signaling pathways. This leads to a violation of the homeostasis of periodontal tissues. Components of the extracellular matrix (ECM) are an important part of biomaterials used for the repair of periodontal tissue. The purpose of this study was to evaluate the components of the effect of ECM (hyaluronic acid (HA), fibronectin (Fn), and laminin (Lam)) on the osteogenic and odontogenic differentiation of periodontal ligament stem cells (PDLSCs) in the collagen I hydrogel under conditions of disruption of the Wnt/β-catenin and TGF-β signaling pathways. The study showed that the addition of components of the ECM restored the expression of odontogenic markers in PDLSCs, which was absent during inhibition of the canonical Wnt signaling pathway, and their multidirectional effect on the secretion of transforming growth factor-β1 (TGF-β1) and bone morphogenetic protein 2 (BMP-2). Fn and Lam suppressed the expression of odontogenic markers in PDLSCs against the background of inhibition of the TGF-β signaling pathway. The addition of HA under the conditions of the TGF-β signaling pathway improved BMP-2 secretion, preserving odontogenic differentiation. Thus, our results demonstrated that disruption of the Wnt/β-catenin and TGF-β signaling pathways causes disorders in the differentiation of PDLSCs, preventing the regeneration of periodontal tissues. This should be taken into account when developing multicomponent scaffolds that recapitulate the ECM microenvironment at endogenic regeneration of the periodontium. Inclusion of hyaluronic acid as one of these components may enhance the therapeutic effect of such biomaterials.
A case of familial partial lipodystrophy type 2 masquerading as Cushing syndrome: Explaining an atypical phenotype by whole-exome sequencingPerez-Dionisio, Hinojosa-Alvarez, Chavez-Santoscoy
et alArch Endocrinol Metab (2025) 69 (1), e240293
Abstract: Familial partial lipodystrophy type 2 is a rare disease, particularly when it is caused by nonclassical gene variants. A high index of suspicion is essential for a timely diagnosis. We present the case of a 32-year-old woman, referred to evaluation of a possible Cushing syndrome, which was clinically and biochemically ruled out. Yet, due to the finding of a rather abnormal fat distribution during physical examination, the diagnosis of lipodystrophy was cogitated. Whole-exome sequencing revealed a missense variant of exon 11 R582H of the gene encoding Laminin A (rs57830985,c.1745G>A, p.Arg582His). The patient presented some clinical and biochemical characteristics discordant with those previously reported in patients harboring other classical variants of this gene.
A cadaveric study of the innervation of the anterior compartment of the kneeSuresh, Buddhiraju, Kuo
et alArch Orthop Trauma Surg (2025) 145 (1), 211
Abstract: Anterior knee pain can significantly affect the quality of life of those living with it. One approach to addressing anterior knee pain involves the selective denervation of the patella to reduce afferent pain transmission, but there has been no consensus on the number, location, or origin of the nerves innervating the patella. In this study, we review existing literature on anterior knee innervation and present findings from our cadaveric dissection to provide a detailed description of the innervation of the anterior knee joint.Two independent authors reviewed the literature on anterior knee innervation from PubMed and Embase, and a sub-search was conducted on the relationship between the infrapatellar branch of the saphenous nerve (IPBSN) and the anterior knee compartment. Subsequently, two fresh-frozen cadavers were dissected to determine whether the saphenous nerve innervates the anterior knee compartment and to confirm, through tissue biopsies stained with laminin and beta-III-tubulin, whether previously described nerves innervate the patella.A total of 463 and 304 entries on patellar innervation and saphenous nerve anatomy, respectively, were identified through PubMed and Embase. Descriptions of the nerves innervating the patella were found to be inconsistent and are summarized. No studies identified branches of the IPBSN directly innervating the patella or patellar tendon. On cadaveric dissection, we found that anterior knee innervation comprised the nerves within the distal vastus medialis and lateralis muscles, the medial and lateral retinacular nerves, and occasionally a branch of the IPBSN that innervated the inferomedial anterior knee skin.This study is the first to provide histological confirmation of patellar innervation by the IPBSN. Our findings suggest that an approach based on a positive response to differential nerve blocks, followed by resection of the nerves implicated in that anterior compartment knee pain, may be more effective in treating persistent anterior knee pain than circumferential electroablation of the patella or routine resection of the IPBSN.Level III.© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Gravitational forces and matrix stiffness modulate the invasiveness of breast cancer cells in bioprinted spheroidsBreideband, Wächtershäuser, Sarkar
et alMater Today Bio (2025) 31, 101640
Abstract: The progression of breast cancer is influenced by the stiffness of the extracellular matrix (ECM), which becomes stiffer as cancer advances due to increased collagen IV and laminin secretion by cancer-associated fibroblasts. Intriguingly, breast cancer cells cultivated in two-dimensions exhibit a less aggressive behavior when exposed to weightlessness, or microgravity conditions. This study aims to elucidate the interplay between matrix stiffness and microgravity on breast cancer progression. For this purpose, three-dimensional spheroids of breast cancer cell lines (MCF-7 and MDA-MB-231) were formed. These spheroids were subsequently bioprinted in hydrogels of varying stiffness, obtained by the mixing of gelatin methacrylate and poly(ethylene) glycol diacrylate mixed at different ratios. The constructs were printed with a custom stereolithography (SLA) bioprinter converted from a low-cost, commercially available 3D printer. These bioprinted structures, encapsulating breast cancer spheroids, were then placed in a clinostat (microgravity simulation device) for a duration of seven days. Comparative analyses were conducted between objects cultured under microgravity and standard earth gravity conditions. Protein expression was characterized through fluorescent microscopy, while gene expression of MCF-7 constructs was analyzed via RNA sequencing. Remarkably, the influence of a stiffer ECM on the protein and gene expression levels of breast cancer cells could be modulated and sometimes even reversed in microgravity conditions. The study's findings hold implications for refining therapeutic strategies for advanced breast cancer stages - an array of genes involved in reversing aggressive or even metastatic behavior might lead to the discovery of new compounds that could be used in a clinical setting.© 2025 The Authors.
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