In this study of the alterations of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts in Osteoarthritis (OA), the levels of GPCs and Notum in the plasma of 25 patients and 24 healthy subjects were measured. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured over a period of 21 days using both a culture medium and an osteogenic medium. Protein and gene expression levels of GPCs and Notum were determined using ELISA and qPCR at 0, 7, 14 and 21 days. GPC5 and Notum levels decreased in the plasma of OA patients, while the BM-MSCs of OA patients showed downexpression of GPC6 and upregulation of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPCs 2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in patients with OA. Furthermore, the protein levels of GPC2, GPC5 and Notum decreased, while the levels of GPC3 increased. Glypicans and Notum were altered in BM-MSCs and during osteogenic differentiation from patients with OA. The alterations found point to GPC5 and Notum as new candidate biomarkers of OA pathology.

Study of alterations in Osteoarthritis (OA) of Glypicans 1 to 6 (GPCs) and Notum in plasma, bone marrow mesenchymal stromal cells (BM-MSCs) and osteoblasts. Plasma levels of GPCs and Notum were measured of 25 patients and 24 healthy subjects. In addition, BM-MSCs from eight OA patients and eight healthy donors were cultured during 21 days with culture me-dium and osteogenic medium. Protein and gene expression levels of GPCs and Notum were de-termined by ELISA and qPCR at 0, 7 ,14 and 21 days. GPC5 and Notum have been found de-creased in OA patients’ plasma. OA BM-MSCs showed downexpression of GPC6 and upregula-tion of Notum. A decrease in GPC5 and Notum proteins and an increase in GPC3 were found. During osteogenic differentiation, elevated GPC2, 4, 5, 6 and Notum mRNA levels and decreased GPC3 were observed in OA. Furthermore, the protein levels of GPC2, GPC5 and Notum de-creased and GPC3 increased. Glypicans and Notum are altered in BM-MSCs and during osteo-genic differentiation from patients with OA. Furthermore, GPC5 and Notum can be proposed as new biomarkers of the pathology. The alterations found indicate that Notum could be a prom-ising therapeutic strategy for Osteoarthritis.

Osteoarthritis (OA) is the most common multifactorial joint disease characterized by progressive cartilage degradation and impaired tissue repair. Osteochondral defects represent a major clinical challenge within OA, as damage to cartilage and underlying bone can initiate degenerative changes and contribute to joint deterioration. The Wnt/β-catenin signaling pathway plays an important role in OA pathogenesis, and its dysregulation contributes to chondrocyte catabolism and cartilage loss. NOTUM, an extracellular Wnt inhibitor, has emerged as a potential therapeutic modulator capable of restoring signaling balance and promoting cartilage homeostasis. This study aimed to evaluate the efficacy of NOTUM compared with hyaluronic acid (HA), human adipose-derived mesenchymal stromal cells (hAd-MSCs), and Colchicine in a rabbit osteochondral defect model relevant to osteoarthritis. Twenty-seven New Zealand White rabbits underwent standardized femoral condyle injury and received single-dose treatments. Serum levels of cartilage biomarkers—Procollagen Type IIA N-terminal Propeptide (PIIANP) and Cartilage Oligomeric Matrix Protein (COMP)—were measured by ELISA at 4, 6, and 8 weeks post-surgery, and histological repair at week 12 was assessed using the modified O’Driscoll scoring system. NOTUM treatment significantly increased PIIANP and decreased COMP levels compared with HA, indicating enhanced cartilage synthesis and reduced degradation. Histological scores confirmed superior surface morphology and tissue composition in NOTUM-treated joints. These findings suggest that NOTUM performs a protective and regenerative effect through Wnt/β-catenin modulation, supporting the conclusion that it enhances osteochondral defect repair and motivating further studies of NOTUM as an OA therapy.

There are studies which indicate that some sulfonamide derivatives can produce changes in the cardiovascular system; however, their biological activity on perfusion presure and coronary resistance is not clear. The aim of this research was to evaluate the effect exerted by benzenesulfonamide, and their derivatives (2,5-dichloro- N-(4-nitro-phenyl)-benzene-sulfonamide, 2-hydrazino-carbonyl-benzenesulfonamide, 4-(2-amino-ethyl)-benze- ne-sulfonamide, and 4-[3-(4-nitro-phenyl)-ureido]-benzene- sulfonamide) on perfusion pressure and coronary reistance. To evaluate the biological activity of benzenesulfonamide and their derivatives on perfusion pressure and coronary reistance an isolated rat heart model was used. Furthermore, theoretical interaction of 4-(2-amino-ethyl)-benzenesul- fonamide with Calcium channel surface was determined using 6jp5 protein, nifedipine, amlodipine, verapamil and BayK 8644 as theoretical tools in a DockingServer program. The Results showed that 4-(2-amino-ethyl)-ben- zenesulfonamide decreased perfusion pressure and coronary resistance compared to benzenesulfonamide, 2,5-dichloro- N-(4-nitro-phenyl)-benzene-sulfonamide, 2-hydrazinocar- bonyl-benze-nesulfonamide, 4-[3-(4-nitro-phenyl)-ureido]- benenesulfonamide and the control conditions. Besides, theoretical data suggest that 4-(2-aminoethyl)benzenesulfo- namide could interact with aminoacid residues such as Glu614 and Ala320 involved in 6jp5 protein surface. This phenomenon could result in an ligand-Calcium channel complex formation to produce a decrease in perfusion pressure and vascular resistance. It is noteworthy that biological and experimental models used in this study is an invaluable research tool for investigating questions across the spectrum of physiologic functions of cardiovascular system such as perfusion pressure and coronary resistance Existem estudos que indicam que alguns derivados das sulfonamidas podem produzir alterações no sistema cardiovascular entretanto, sua atividade biológica na pressão de perfusão e na resistência coronariana não está clara. O objetivo desta pesquisa foi avaliar o efeito exercido pela benzenossulfonamida e seus derivados (2,5-dicloro-N-(4-nitro-fenil)-benzeno-sulfonamida, 2-hidrazino-carbonil-benzenossulfonamida, 4-(2-amino- etil)-benzeno-sulfonamida e 4-[3-(4-nitro-fenil)-ureido]-benzeno-sulfonamida) na pressão de perfusão e na resistência coronariana. Para avaliar a atividade biológica da benzenossulfonamida e seus derivados na pressão de perfusão e na resistência coronariana, foi utilizado um modelo isolado de coração de rato. Além disso, a interação teórica da 4-(2-amino-etil)-benzenossulfonamida com a superfície do canal de Cálcio foi determinada usando a proteína 6jp5, nifedipina, amlodipina, verapamil e BayK 8644 como ferramentas teóricas em um programa DockingServer. Os resultados mostraram que a 4-(2-amino-etil)-benzenossulfonamida diminuiu a pressão de perfusão e a resistência coronariana em comparação com a benzenossulfonamida, 2,5-dicloro-N-(4-nitro-fenil)-benzeno-sulfonamida, 2-hidrazinocarbonil-benze-nessulfonamida, 4-[3-(4-nitro- fenil)-ureido]-benenossulfonamida e as condições de controlo. Além disso, dados teóricos sugerem que a 4-(2-aminoetil)benzenossulfonamida poderia interagir com resíduos de aminoácidos como Glu614 e Ala320 envolvidos na superfície da proteína 6jp5. Este fenômeno pode resultar na formação de um complexo ligante-canal de Cálcio para produzir uma diminuição na pressão de perfusão e na resistência vascular. Vale ressaltar que, os modelos biológicos e experimentais utilizados neste estudo são uma ferramenta de pesquisa inestimável para investigar questões em todo o espectro de funções fisiológicas do sistema cardiovascular, como pressão de perfusão e resistência coronariana.