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1. Neutral detergent fibre in piglet diets: digestibility, performance, and deposition of body nutrients

Author

RAFAEL C. NEPOMUCENO, PEDRO H. WATANABE, EDNARDO R. FREITAS, LUIZ E. DE CARVALHO, EMANUELA L. DE OLIVEIRA, THALLES R. GOMES, GERMANA C. AGUIAR, RAYSSA S. CANDIDO, JORDÂNIA L. FERREIRA, and ALINI M. VEIRA

Subjects
dietary fibre, retention of nutrients, pigs, post-weaning, Science
Abstract

ABSTRACT A total 120 piglets with an average live weight of 7.00 kg, weaned at 21 days, were used to evaluate the effect of neutral detergent fibre levels on the digestibility of nutrients and energy from the diets, productive performance, and the composition and rate of deposition of nutrients and energy in the bodies of piglets in the nursery phase. The animals were distributed according to a randomized-block design into five treatments, which consisted of neutral detergent fibre levels, with six replicates and four animals per plot. A quadratic effect was detected for the digestibility coefficients of nutrients and energy, feed intake and weight gain. The increase in fibre level promoted a linear increase in fat content in the carcass, blood, and body, whereas the energy in the carcass, organs, and body showed an inverse response. The results showed a quadratic effect on the nutrient deposition rate in the carcass, organs and body. In conclusion, the best digestibility of nutrients and energy from the diet is obtained with 10-11.5% neutral detergent fibre, as higher weight gain and greater protein deposition in the body are achieved at neutral detergent fibre levels of 10.6% and 10.3%, respectively.

Published
2017
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2. Stimulatory effects of creatine on metabolic activity, differentiation and mineralization of primary osteoblast-like cells in monolayer and micromass cell cultures

Author

Gerber I., ap Gwynn I., Alini M., and Wallimann T.

Subjects
Diseases of the musculoskeletal system, RC925-935, Orthopedic surgery, RD701-811
Abstract

The effects of creatine (Cr) supplementation on primary rat osteoblast-like cells cultured as monolayer and micromass were investigated. Cr was added to the medium at concentrations of either 10 or 20 mM. At various time points, the cell cultures were analyzed morphologically, metabolically and biochemically. The degree of differentiation of primary osteoblast-like cell cultures was higher in micromass cultures compared to monolayer cultures, as judged by alkaline phosphatase (;ALP) activity and extent of mineralization. In both culture systems, Cr supplementation showed positive effects, which were dependent on the organizational level of the osteoblast-like cells in such a way that the cells in monolayer culture showed significantly increased metabolic activity, ALP activity and mineralization in the presence of Cr than without the supplement. In micromass cultures, Cr also significantly enhanced ALP activity and mineralization, without affecting metabolic activity. The effect of Cr on ALP activity was more pronounced at higher concentrations of Cr, but 20 mM Cr already showed some adverse effects on cell viability. In conclusion, chemically pure Cr added to low serum cell culture medium has a stimulatory effect on metabolic activity, differentiation and mineralization of osteoblast-like cells indicating that Cr supplementation could also be used as a potential clinical intervention to stimulate cell growth, differentiation and mineralization during bone repair in vivo.

Published
2005

22. Secreted miR‐153 Controls Proliferation and Invasion of Higher Gleason Score Prostate Cancer

Author

Bertoli, G, Panio, A, Cava, C, Gallivanone, F, Alini, M, Strano, G, Molfino, F, Brioschi, L, Viani, P, Porro, D, Bertoli, G, Panio, A, Cava, C, Gallivanone, F, Alini, M, Strano, G, Molfino, F, Brioschi, L, Viani, P, and Porro, D

Abstract

Prostate cancer (PC) is a male common neoplasm and is the second leading cause of cancer death in American men. PC is traditionally diagnosed by the evaluation of prostate secreted antigen (PSA) in the blood. Due to the high levels of false positives, digital rectal examination and transrectal ultrasound guided biopsy are necessary in uncertain cases with elevated PSA levels. Nevertheless, the high mortality rate suggests that new PC biomarkers are urgently needed to help clinical diagnosis. In a previous study, we have identified a network of genes, altered in high Gleason Score (GS) PC (GS ≥ 7), being regulated by miR‐153. Until now, no publication has explained the mechanism of action of miR‐153 in PC. By in vitro studies, we found that the overexpression of miR‐ 153 in high GS cell lines is required to control cell proliferation, migration and invasion rates, targeting Kruppel‐like factor 5 (KLF5). Moreover, miR‐153 could be secreted by exosomes and microvesicles in the microenvironment and, once entered into the surrounding tissue, could influence cellular growth. Being upregulated in high GS human PC, miR‐153 could be proposed as a circulating biomarker for PC diagnosis.

Published
2022

31. Serum biomarkers for Modic changes in patients with chronic low back pain

Author

Karppinen, J. (Jaro), Koivisto, K. (Katri), Ketola, J. (Jukka), Haapea, M. (Marianne), Paananen, M. (Markus), Herzig, K. (Karl‑Heinz), Alini, M. (Mauro), Lotz, J. (Jeffrey), Dudli, S. (Stefan), Samartzis, D. (Dino), Risteli, J. (Juha), Majuri, M. (Marja‑Leena), Alenius, H. (Harri), Kyllönen, E. (Eero), Järvinen, J. (Jyri), Niinimäki, J. (Jaakko), Grad, S. (Sibylle), Karppinen, J. (Jaro), Koivisto, K. (Katri), Ketola, J. (Jukka), Haapea, M. (Marianne), Paananen, M. (Markus), Herzig, K. (Karl‑Heinz), Alini, M. (Mauro), Lotz, J. (Jeffrey), Dudli, S. (Stefan), Samartzis, D. (Dino), Risteli, J. (Juha), Majuri, M. (Marja‑Leena), Alenius, H. (Harri), Kyllönen, E. (Eero), Järvinen, J. (Jyri), Niinimäki, J. (Jaakko), and Grad, S. (Sibylle)

Abstract

Purpose: Lumbar Modic change (MC) can serve as a diagnostic marker as well as an independent source of chronic low back pain (CLBP). This study aimed to test for the existence of serum biomarkers in CLBP patients with MC. Methods: Age- and sex-matched CLBP patients with confirmed MC on lumbar MRI (n = 40) and pain-free controls (n = 40) were assessed. MC was classified into M1, predominating M1, predominating M2 and M2. MC volumes were calculated. Fasting blood samples were assessed for inflammatory mediators, signalling molecules, growth factors and bone turnover markers. Serum concentrations of 46 biomarkers were measured. Results: Median concentrations of interleukin (IL)-15 (p < 0.001), IL-8 (p < 0.001), tumour necrosis factor (TNF)-alpha (p < 0.001), Eotaxin-1 (p < 0.05), Eotaxin-3 (p < 0.001), monocyte chemotactic protein (MCP)-1 (p < 0.05), macrophage inflammatory protein (MIP)-1alpha (p < 0.01), TEK receptor tyrosine kinase (Tie)-2 (p < 0.001), vascular cell adhesion molecule (VCAM)-1 (p < 0.001), RANTES (p < 0.001), C telopeptide of type I collagen (CTX)-1 (p < 0.001), vascular endothelial growth factor (VEGF)-C (p < 0.001), VEGF-D (p < 0.05), fms-related tyrosine kinase (Flt)-1 (p < 0.01) and intercellular adhesion molecule (ICAM)-1 (p < 0.01) were significantly higher among controls. IL-1sRII (23.2 vs. 15.5 ng/ml, p < 0.001) and hepatocyte growth factor (HGF)-1 (169 vs. 105 pg/ml, p < 0.01) concentrations were significantly higher among patients. Type or volume of MC was not associated with biomarker concentrations. Conclusions: This is the first study to assess the blood serum biomarker profile in individuals with CLBP with MC. Several biomarkers were suppressed, while two markers (IL-1sRII and HGF) were elevated among MC patients, irrespective of MC type or size, with CLBP compared with asymptomatic controls.

Published
2021

32. In vivo Analyse der Biokompatibilität und Vaskularisierung elastischer Polyurethan-Scaffolds für das Tissue Engineering

Author

Strohe, A., Laschke, M. W., Eglin, D., Verrier, S., Alini, M., Scheuer, C., Menger, M. D., Buhr, H. J., editor, Hölscher, A., editor, Izbicki, J. R., editor, Jauch, K. W., editor, Post, S., editor, Allgayer, H., editor, Bartsch, D. K., editor, Fries, H., editor, Ghadimi, B. M., editor, Habermann, J. K., editor, Kalthoff, H., editor, Schackert, H. K., editor, Bruns, C. J., editor, Duda, D. N., editor, Fändrich, F., editor, Heberer, M., editor, Nüssler, A. K., editor, Stark, G. B., editor, Brückner, U. B., editor, Ertel, W., editor, Faist, E., editor, Heidecke, C. D., editor, Kalff, J. C., editor, Menger, M. D., editor, Schade, U. F., editor, Vollmar, B., editor, Bechstein, W. O., editor, Klar, E., editor, Klempnauer, J., editor, Minor, T., editor, Neuhaus, P., editor, Schmidt, J., editor, Langer, S., editor, Laschke, M. W., editor, Machens, H. G., editor, Steinau, H. U., editor, Südkamp, N., editor, Vogt, P., editor, Berger, D., editor, Klinge, U., editor, Schachtrupp, A., editor, Schilling, M. K., editor, Schumpelick, V., editor, Altendorf-Hofmann, A., editor, Bollschweiler, E., editor, Bruch, H. -P., editor, Lehnert, T., editor, Lorenz, W., editor, Neugebauer, E., editor, Ohmann, C., editor, Seiler, C. M., editor, Becker, H., editor, Betzler, M., editor, Bittner, R., editor, Broelsch, C., editor, Büchler, M. W., editor, Bumm, R., editor, Dralle, H., editor, Friess, H., editor, Frilling, A., editor, Germer, C. T., editor, Hopt, U., editor, Jonas, S., editor, Jost, J., editor, Markus, B., editor, Raab, H. R., editor, Reith, H. B., editor, Schlag, P. M., editor, Teichmann, W., editor, Uhl, W., editor, Wenisch, H., editor, and Zornig, C., editor

Published
2009
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33. Evaluation of biomimetic hyaluronic-based hydrogels with enhanced endogenous cell recruitment and cartilage matrix formation

Author

Vainieri, M.L. (Maria Letizia), Lolli, A. (Andrea), Kops, N. (Nicole), D'Atri, D. (D.), Eglin, D. (David), Yayon, A. (A.), Alini, M. (Mauro), Grad, S. (S.), Sivasubramaniyan, K. (Kavitha), Osch, G.J.V.M. (Gerjo) van, Vainieri, M.L. (Maria Letizia), Lolli, A. (Andrea), Kops, N. (Nicole), D'Atri, D. (D.), Eglin, D. (David), Yayon, A. (A.), Alini, M. (Mauro), Grad, S. (S.), Sivasubramaniyan, K. (Kavitha), and Osch, G.J.V.M. (Gerjo) van

Abstract

Biomaterials play a pivotal role in cell-free cartilage repair approaches, where cells must migrate through the scaffold, fill the defect, and then proliferate and differentiate facilitating tissue remodeling. Here we used multiple assays to test the influence of chemokines and growth factors on cell migration and cartilage repair in two different hyaluronan (HA)-based hydrogels. We first investigated bone marrow Mesenchymal Stromal Cells (BMSC) migration in vitro, in response to different concentrations of platelet-derived growth factor-BB (PDGF-BB), chemokine ligand 5 (CCL5/RANTES) and stromal cell-derived factor 1 (SDF-1), using a 3D spheroid-based assay. PDGF-BB was selected as most favourable chemotactic agent, and MSC migration was assessed in the context of physical impediment to cell recruitment by testing Fibrin-HA and HA-Tyramine hydrogels of different cross-linking densities. Supplementation of PDGF-BB stimulated progressive migration of MSC through the gels over time. We then investigated in situ cell migration into the hydrogels with and without PDGF-BB, using a cartilage-bone explant model implanted subcutaneously in athymic mice. In vivo studies show that when placed into an osteochondral defect, both hydrogels supported endogenous cell infiltration and provided an amenable microenvironment for cartilage production. These processes were best supported in Fibrin-HA hydrogel in the absence of PDGF-BB. This study used an advanced preclinical testing platform to select an appropriate microenvironment provided by implanted hydrogels, demonstrating that HA-based hydrogels can promote the initial and critical step of endogenous cell recruitment and circumvent some of the clinical challenges in cartilage tissue repair. Statement of significance: The challenge of articular cartilage repair arises from its complex structure and architecture, which confers the unique mechanical behavior of the extracellular matrix. The aim of our research is to identify biomater

Published
2020
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34. Enhanced chondrogenic phenotype of primary bovine articular chondrocytes in Fibrin-Hyaluronan hydrogel by multi-axial mechanical loading and FGF18

Author

Antunes, B.P. (Bernardo P.), Vainieri, M.L. (Maria Letizia), Alini, M. (Mauro), Monsonego-Ornan, E. (Efrat), Grad, S. (Sibylle), Yayon, A. (Avner), Antunes, B.P. (Bernardo P.), Vainieri, M.L. (Maria Letizia), Alini, M. (Mauro), Monsonego-Ornan, E. (Efrat), Grad, S. (Sibylle), and Yayon, A. (Avner)

Abstract

Current treatments for cartilage lesions are often associated with fibrocartilage formation and donor site morbidity. Mechanical and biochemical stimuli play an important role in hyaline cartilage formation. Biocompatible scaffolds capable of transducing mechanical loads and delivering bioactive instructive factors may better support cartilage regeneration. In this study we aimed to test the interplay between mechanical and FGF-18 mediated biochemical signals on the proliferation and differentiation of primary bovine articular chondrocytes embedded in a chondro-conductive Fibrin-Hyaluronan (FB/HA) based hydrogel. Chondrocytes seeded in a Fibrin-HA hydrogel, with or without a chondro-inductive, FGFR3 selective FGF18 variant (FGF-18v) were loaded into a joint-mimicking bioreactor applying controlled, multi-axial movements, simulating the natural movements of articular joints. Samples were evaluated for DNA content, sulphated glycosaminoglycan (sGAG) accumulation, key chondrogenic gene expression markers and histology. Under moderate loading, samples produced particularly significant amounts of sGAG/DNA compared to unloaded controls. Interestingly there was no significant effect of FGF-18v on cartilage gene expression at rest. Following moderate multi-axial loading, FGF-18v upregulated the expression of Aggrecan (ACAN), Cartilage Oligomeric Matrix Protein (COMP), type II collagen (COL2) and Lubricin (PRG4). Moreover, the combination of load and FGF-18v, significantly downregulated Matrix Metalloproteinase-9 (MMP-9) and Matrix Metaloproteinase-13 (MMP-13), two of the most important factors contributing to joint destruction in OA. Biomimetic mechanical signals and FGF-18 may work in concert to support hyaline cartilage regeneration and repair. Statement of significance: Articular cartilage has very limited repair potential and focal cartilage lesions constitute a challenge for current standard clinical procedures. The aim of the present research was to explore novel proc

Published
2020
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38. The Effect of Zoledronic Acid on Serum Biomarkers among Patients with Chronic Low Back Pain and Modic Changes in Lumbar Magnetic Resonance Imaging

Author

Koivisto, K. (Katri), Karppinen, J. (Jaro), Marianne Haapea, M. H. (Marianne Haapea), Järvinen, J. (Jyri), Kyllönen, E. (Eero), Tervonen, O. (Osmo), Niinimäki, J. (Jaakko), Alini, M. (Mauro), Lotz, J. (Jeffrey), Dudli, S. (Stefan), Samartzis, D. (Dino), Risteli, J. (Juha), Majuri, M.-L. (Marja-Leena), Alenius, H. (Harri), Grad, S. (Sibylle), University of Zurich, and Koivisto, Katri

Subjects
Modic change, serum biomarkers, Pain Research, Clinical Trials and Supportive Activities, 10051 Rheumatology Clinic and Institute of Physical Medicine, Evaluation of treatments and therapeutic interventions, 610 Medicine & health, 1308 Clinical Biochemistry, serum biomarkersm magnetic resonance imaging, zoledronic acid, Clinical Research, 6.1 Pharmaceuticals, Musculoskeletal, chronic low back pain, randomized trial, magnetic resonance imaging, Chronic Pain
Abstract

The aim of the current study was to compare changes in serum biomarkers, including inflammatory mediators, signaling molecules, growth factors and markers of bone turnover after a single intravenous infusion of 5 mg zoledronic acid (ZA, a long-acting bisphosphonate; n = 20) or placebo (n = 20) among patients with Modic changes (MC) and chronic low back pain in a randomized controlled design. The MCs were classified into M1, predominating M1, predominating M2, and M2. We measured the serum concentrations of 39 biomarkers at baseline, and one month and one year after treatment. After Benjamini–Hochberg (B–H) correction, we observed significant differences in three biomarkers over one year: Interferon-γ-inducible protein (IP-10) had risen in the ZA group (p = 0.005), whereas alkaline phosphatase (AFOS) and intact procollagen I N-terminal propeptide (iPINP) had significantly decreased in the ZA group, but had not changed in the placebo group (p < 0.001 for both). Change in iPINP correlated with change in the volume of all MC and M1 lesions. ZA downregulated bone turnover markers as expected and, surprisingly, increased the chemokine IP-10 relative to placebo treatment. This adds to our knowledge of the effects of ZA on MC and the biomarkers that signal this process.

Published
2019

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