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Concavities of Crystalline Sintered Hydroxyapatite-Based Macroporous Bioreactors Initiate the Spontaneous Induction of Bone Formation
Published in Ugo Ripamonti, The Geometric Induction of Bone Formation, 2020
Various up and down expression patterns are reported by a day-time study and by TCP-B and TCP-S substrata using both basal and osteogenic media (Zhang et al. 2017). The expression patterns of the Osteocalcin gene on days 4 and 7 in vitro by TCP-S constructs are noteworthy (Zhang et al. 2017). The Osteopontin gene is also shown to be expressed increasingly from day 4 to day 14 during in vitro studies on TCP-S substrata (Zhang et al. 2017). It should be noted, however, that Osteopontin gene and gene products are not differentiating factors but merely structural assemblages of few skeletal cells lacking altogether differentiating and morphogenetic capacities.
Renal Pathophysiology
Published in Manit Arya, Taimur T. Shah, Jas S. Kalsi, Herman S. Fernando, Iqbal S. Shergill, Asif Muneer, Hashim U. Ahmed, MCQs for the FRCS(Urol) and Postgraduate Urology Examinations, 2020
Herman S. Fernando, Mohamed Yehia Abdallah, Iqbal S. Shergill
Tamm-Horsfall protein, which is the most abundant urinary protein, is secreted by renal epithelial cells in the thick ascending limb and the distal convoluted tubule as a membrane-anchored protein. It is a potent inhibitor of calcium oxalate monohydrate crystal aggregation, but not growth. Nephrocalcin, an acidic glycoprotein, is synthesised in the proximal renal tubules and the thick ascending limb. Osteopontin, or uropontin, is an acidic phosphorylated glycoprotein expressed in bone matrix and renal epithelial cells of the ascending limb of the loop of Henle and the distal tubule. Glycosaminoglycans, acid mucopolysaccharides, and RNA are examples of polyanions that have been shown to inhibit crystal nucleation and growth. The inhibitory activity of magnesium is derived from its complexation with oxalate, which reduces ionic oxalate concentration and calcium oxalate supersaturation. Among the glycosaminoglycans, heparin sulfate interacts most strongly with calcium oxalate monohydrate crystals.
Recurrence of endometriosis
Published in Seema Chopra, Endometriosis, 2020
SICAM-1 increases in early stages and decreases in stage III/IV endometriosis [31]. Osteopontin, a cell adhesion molecule, increases in all stages [32]. Matrix metalloproteinases (MMPs) facilitate invasion of the peritoneum by endometrial fragments. MMP-2, -9 are significantly higher in endometriosis cases [33–35].
Clinical utility of checkpoint inhibitors against metastatic bladder cancer: overcoming challenges to find a way forward
Published in Expert Opinion on Biological Therapy, 2023
Andreia Bilé-Silva, Antonio Lopez-Beltran, Ana Blanca, Fernando Lopez-Rios, Enrique Gómez-Gómez, Alessia Cimadamore, Rodolfo Montironi, Nuno Vau, Liang Cheng
Research of new drugs targeting different molecules and pathways is ongoing with promising results. Osteopontin (OPN) has been recently investigated because of its association with cancer progression; it is still under research. However, as originally reported, OPN expression was significantly higher in bladder cancer specimens with higher T-stage or tumor grades, which showed poorer survival. The same study reported matrix metallopeptidase 9 (MMP9) and S100 calcium-binding protein A8 (S100A8) as downstream factors for OPN in bladder cancer specimens and cell lines. The expression of OPN was significantly positively associated with that of MMP9, and S100A8, with a higher level being associated with a higher T-stage and tumor grade and a shorter survival time in bladder cancer patients. Thus, OPN, MMP9, and S100A8 may be regarded as prognostic markers and therapeutic targets in bladder cancer [73].
Place in therapy of anti-IL-17 and 23 in psoriasis according to the severity of comorbidities: a focus on cardiovascular disease and metabolic syndrome
Published in Expert Opinion on Biological Therapy, 2022
Emanuele Trovato, Pietro Rubegni, Francesca Prignano
A pathogenetic link between psoriasis and DM II could be primarily referred to an increased expression of TNF-α that, by reducing the action of tyrosine kinase, increases insulin resistance. Inflammation reduces insulin sensitivity and insulin receptor activity (IRS-1) through cytokines (IL-17, IL-6, TNF, and IL-1) and stress pathways (hypoxia, ROS, endoplasmic reticulum activation, lipids, and fatty acids) [37]. IL-17 inhibits IRS-1 (insulin receptor substrate) phosphorylation directly via IkB kinase/nuclear factor-kappa B (IKK/NFkb) pathway and indirectly via c-Jun N-terminal kinase (JNK), leading to incorrect insulin phosphorylation, less effective insulin signal, glucose uptake, increased insulin resistance, obesity, and diabetes [45]. The correlation could be explained by the potentially beneficial role of metformin. Its anti-inflammatory mechanism of action is based on the activation of AMPK and the inhibition of the mTOR pathway. Metformin acts on the dysregulation of mitochondrial autophagy, increasing its susceptibility to develop inflammatory diseases. Osteopontin is secreted by T lymphocytes and participates in inflammation, being secreted by T lymphocytes. In psoriasis, osteopontin acts by promoting neo-angiogenesis and cell uptake. Metformin attenuates the upregulation of osteopontin and protein 1-induced monocyte chemotaxis [46]. For all these reasons, we think it could be useful to add diabetes screening before starting biologics. We could so consider anti-IL-17/IL-23 as first choice in these patients.
Calcitonin-loaded octamaleimic acid–silsesquioxane nanoparticles in hydrogel scaffold support osteoinductivity in bone regeneration
Published in Pharmaceutical Development and Technology, 2021
Saeedeh Ahmadipour, Jaleh Varshosaz, Batool Hashemibeni, Leila Safaeian, Maziar Manshaei, Akram Sarmadi
The osteocalcin expression was 5.5-fold higher on day 7 and 2.7-fold greater on day 10 for this scaffold in comparison with chitosan only. Also, a significant higher expression of COL1A1 was observed on the 7th and 10th days for the chitosan/nano-hydroxyapatite/collagen scaffold compared to chitosan only (Chen et al. 2012). Mizuno and Kuboki (Mizuno and Kuboki 2001) reported that the expression of the osteopontin gene increased time-dependently during osteoblastic differentiation. Osteocalcin was expressed in cells that formed mineralized tissues. The effect of local administration of sCT and alendronate on the bone formation marker osteocalcin was investigated on sheep, and the researchers showed that bone defects were filled with injectable gelatin sponges containing sCT (Wafaa and Hassouni 2014), which resulted in higher levels of osteocalcin as an indicative biomarker of the activity of osteoblasts and osteoclasts.