Collagen type XV and the ‘osteogenic status’

Lisignoli, Gina; Lambertini, Elisabetta; Manferdini, Cristina; Gabusi, Elena; Penolazzi, Letizia; Paolella, Francesca; Angelozzi, Marco; Casagranda, Veronica; Piva, Roberta

doi:10.1111/jcmm.13137

Cited by 27 publications

(26 citation statements)

References 52 publications

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“…We recently demonstrated that a chondroitin sulphate modified glycoprotein, the ColXV [20,21] is a critical regulatory component of the osteogenic pathway and that its expression in hMSCs is a prerequisite to promote the subsequent deposition of mineral matrix [23]. For the first time we correlated the increase of HIF-1α expression after hypoxia preconditioning with the increase of ColXV.…”

Section: Discussionmentioning

confidence: 80%

“…In order to investigate if hypoxia preconditioning has beneficial effects in making cells more prone to osteo-differentiation, the expression of ColXV, previously identified as predictive marker for selecting hMSCs with high osteo-differentiation potential [23], has been assessed at different levels. As reported in Fig.…”

Section: Colxv Expression In Hypoxia-preconditioned Hmscsmentioning

confidence: 99%

“…hMSCs were extensively characterized as previously reported [23,24]. The cells were grown in α-MEM medium supplemented with 15% fetal bovine serum (FBS) (Euroclone S.p.A., Milan, Italy), penicillin-streptomycin (100 U/ml-100μg/ml) (Sigma-Aldrich, St. Louis, MO, USA).…”

Section: Isolation and Growth Of Hmscsmentioning

confidence: 99%

“…Frozen hMSCs isolated from bone marrow aspirates of 12 healthy donors using Ficoll-Hypaque density gradient (d=1.077 g/ml), as previously described [23], were anonymously selected from the Laboratory repository. hMSCs were extensively characterized as previously reported [23,24].…”

Section: Isolation and Growth Of Hmscsmentioning

confidence: 99%

“…As potential good candidate to analyze in this context we focused on non-fibrillar collagen (Col) XV, a chondroitin sulphate modified glycoprotein belonging to the multiplexin subfamily (multiple triple helix domains with interruptions), recently identified as a novel human osteoblast extracellular matrix (ECM) protein [20][21][22]. In particular, our previous evidence suggests that ColXV may act as an ECM organizer in the early-phases of the osteogenic process and that its expression in hMSCs is a prerequisite to promote the subsequent deposition of mineral matrix [23]. In this study, we further evaluate the role of ColXV testing the hypothesis that hypoxic environment may influence its expression in hMSCs.…”

Section: Introductionmentioning

confidence: 99%

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Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Lambertini

Penolazzi

Angelozzi

et al. 2018

Cell Physiol Biochem

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Background/Aims: Mesenchymal stromal cells (MSCs) hold considerable promise in bone tissue engineering, but their poor survival and potency when in vivo implanted limits their therapeutic potential. For this reason, the study on culture conditions and cellular signals that can influence the potential therapeutic outcomes of MSCs have received considerable attention in recent years. Cell maintenance under hypoxic conditions, in particular for a short period, is beneficial for MSCs, as low O₂ tension is similar to that present in the physiologic niche, however the precise mechanism through which hypoxia preconditioning affects these cells remains unclear. Methods: In order to explore what happens during the first 48 h of hypoxia preconditioning in human MSCs (hMSCs) from bone marrow, the cells were exposed to 1.5% O₂ tension in the X3 Hypoxia Hood and Culture Combo – Xvivo System device. The expression modulation of critical genes which could be good markers of increased osteopotency has been investigated by Western blot, immunufluorescence and ELISA. Luciferase reporter assay and Chromatin immunoprecipitation was used to investigate the regulation of the expression of Collagen type XV (ColXV) gene. Results: We identified ColXV as a new low O₂ tension sensitive gene, and provided a novel mechanistic evidence that directly HIF-1α (hypoxia-inducible factor-1 alpha) mediates ColXV expression in response to hypoxia, since it was found specifically in vivo recruited at ColXV promoter, in hypoxia-preconditioned hMSCs. This finding, together the evidence that also Runx2, VEGF and FGF-2 expression increased in hypoxia preconditioned hMSCs, is consistent with the possibility that increased ColXV expression in response to hypoxia is mediated by an early network that supports the osteogenic potential of the cells. Conclusion: These results add useful information to understand the role of a still little investigated collagen such as ColXV, and identify ColXV as a marker of successful hypoxia preconditioning. As a whole, our data give further evidence that hypoxia preconditioned hMSCs have greater osteopotency than normal hMSCs, and that the effects of hypoxic regulation of hMSCs activities should be considered before they are clinically applied.

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Section: Discussionmentioning

confidence: 80%

Section: Colxv Expression In Hypoxia-preconditioned Hmscsmentioning

confidence: 99%

Section: Isolation and Growth Of Hmscsmentioning

confidence: 99%

Section: Isolation and Growth Of Hmscsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Lambertini

Penolazzi

Angelozzi

et al. 2018

Cell Physiol Biochem

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Specific concentration of hyaluronan amide derivative induces osteogenic mineralization of human mesenchymal stromal cells: Evidence of RUNX2 and COL1A1 genes modulation

Paolella

Gabusi

Manferdini

et al. 2019

J Biomedical Materials Res

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Hyaluronic acid (HA) is an ideal material for tissue regeneration. The aim of this study was to investigate whether a hyaluronan amide derivative (HAD) can enhance the mineralization of human mesenchymal stem cells (hMSCs). Osteogenically induced hMSCs cultured with or without HAD at different concentrations (0.5 mg/ml or 1 mg/ml) were analyzed for mineral matrix deposition, metabolic activity, cellular proliferation, and the expression of 14 osteogenic genes. Unmodified HA (HYAL) was used as control. We demonstrated that only cells treated daily until day 28 with 0.5 mg/ml HAD, but not with 1 mg/ml of HAD and HYAL, showed a significant induction of mineralization at day 14 compared to the osteogenic control group. HAD at both concentrations tested, significantly decreased the expression of the proliferating marker MKI67 at day 2. By contrast, increased metabolic activity was induced only by HYAL from day 14. HAD at both concentrations significantly down modulated SNAI2, DLX5, RUNX2, COL1A1, and IBSP genes, while significantly up regulated COL15A1. The induction of mineralization of 0.5 mg/ml of HAD at day 14 was significantly dependent on a specific modulation of RUNX2 and COL1A1. Our data demonstrate that only 0.5 mg/ml of HAD, but not HYAL, modulated hMSCs osteogenic differentiation, suggesting that the physicochemical features and concentration of HA products could differently affect osteogenic maturation.

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Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

Mongiat,

Pascal,

Poletto

et al. 2024

Proteoglycan Research

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Antiangiogenic therapy is an established method for the treatment of several cancers and vascular‐related diseases. Most of the agents employed target the vascular endothelial growth factor A, the major cytokine stimulating angiogenesis. However, the efficacy of these treatments is limited by the onset of drug resistance. Therefore, it is of fundamental importance to better understand the mechanisms that regulate angiogenesis and the microenvironmental cues that play significant role and influence patient treatment and outcome. In this context, here we review the importance of the three basement membrane (BM) heparan sulfate proteoglycans (HSPGs), namely perlecan, agrin, and collagen XVIII. These HSPGs are abundantly expressed in the vasculature and, due to their complex molecular architecture, they interact with multiple endothelial cell receptors, deeply affecting their function. Under normal conditions, these proteoglycans exert proangiogenic functions. However, in pathological conditions such as cancer and inflammation, extracellular matrix remodeling leads to the degradation of these large precursor molecules and the liberation of bioactive processed fragments displaying potent angiostatic activity. These unexpected functions have been demonstrated for the C‐terminal fragments of perlecan and collagen XVIII, endorepellin, and endostatin. These bioactive fragments can also induce autophagy in vascular endothelial cells which contributes to angiostasis. Overall, BM proteoglycans deeply affect angiogenesis counterbalancing proangiogenic signals during tumor progression and represent possible means to develop new prognostic biomarkers and novel therapeutic approaches for the treatment of solid tumors.

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Collagen type XV and the ‘osteogenic status’

Cited by 27 publications

References 52 publications

Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Hypoxia Preconditioning of Human MSCs: a Direct Evidence of HIF-1α and Collagen Type XV Correlation

Specific concentration of hyaluronan amide derivative induces osteogenic mineralization of human mesenchymal stromal cells: Evidence of RUNX2 and COL1A1 genes modulation

Proteoglycans of basement membranes: Crucial controllers of angiogenesis, neurogenesis, and autophagy

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