Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

Alcorta-Sevillano, Natividad; Macías, Iratxe; Rodrı́guez, Clara I.; Infante, Arantza

doi:10.3390/cells9061330

Cited by 37 publications

(36 citation statements)

References 189 publications

(228 reference statements)

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“…In particular, they are fundamental in bone physiology. Lamin A and C controls bone formation, remodeling, and wound healing by orchestrating osteoblastogenesis and osteoclastogenesis in accordance with ECM biochemical and mechanical properties [ 112 ]. Furthermore, the lamin A/C defective occurrence we observed in dominant and recessive [ 10 ] OI may associate to the impaired transcription that was recently described in OI murine models [ 113 ].…”

Section: Resultsmentioning

confidence: 99%

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

Bini

Schvartz²,

Carnemolla

et al. 2021

IJMS

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Osteogenesis imperfecta (OI) is a heritable disorder that mainly affects the skeleton. The inheritance is mostly autosomal dominant and associated to mutations in one of the two genes, COL1A1 and COL1A2, encoding for the type I collagen α chains. According to more than 1500 described mutation sites and to outcome spanning from very mild cases to perinatal-lethality, OI is characterized by a wide genotype/phenotype heterogeneity. In order to identify common affected molecular-pathways and disease biomarkers in OI probands with different mutations and lethal or surviving phenotypes, primary fibroblasts from dominant OI patients, carrying COL1A1 or COL1A2 defects, were investigated by applying a Tandem Mass Tag labeling-Liquid Chromatography-Tandem Mass Spectrometry (TMT LC-MS/MS) proteomics approach and bioinformatic tools for comparative protein-abundance profiling. While no difference in α1 or α2 abundance was detected among lethal (type II) and not-lethal (type III) OI patients, 17 proteins, with key effects on matrix structure and organization, cell signaling, and cell and tissue development and differentiation, were significantly different between type II and type III OI patients. Among them, some non–collagenous extracellular matrix (ECM) proteins (e.g., decorin and fibrillin-1) and proteins modulating cytoskeleton (e.g., nestin and palladin) directly correlate to the severity of the disease. Their defective presence may define proband-failure in balancing aberrances related to mutant collagen.

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Section: Resultsmentioning

confidence: 99%

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

Bini

Schvartz²,

Carnemolla

et al. 2021

IJMS

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“…Furthermore, we confirmed the effects of combination of low-intensity ultrasound and the G-encapsulated PLGA system for the MSC differentiation by examining the expression levels of Lamin A/C. Since the Lamin A/C is known to become intensively expressed as osteogenic differentiation occurs [ 27 , 28 ], it was selected as a biomarker of early phase of the MSC differentiation into osteoblasts.…”

Section: Introductionmentioning

confidence: 57%

“…In the presence of the mesenchymal stem cells (MSCs), growth factor-containing NPs (G-NPs) were investigated in the aspect of the medium supplement for the osteogenic differentiation. Lamin A/C proteins have been regarded as representative biomarkers expressed in nuclear membranes in the early stages of osteogenic process [ 28 , 41 ]. Previous studies tested usefulness of LIPUS, a type of ultrasound, for enhancing bone formation in vitro and in vivo.…”

Section: Resultsmentioning

confidence: 99%

Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation

et al. 2021

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Mesenchymal stem cells (MSCs) have been extensively used in the tissue regeneration therapy. Ex vivo therapy with well-differentiated osteogenic cells is known as an efficient treatment for musculoskeletal diseases, including rheumatoid diseases. However, along with its high cost, the current therapy has limitations in terms of restoring bone regeneration procedures. An efficient process for the cell differentiation to obtain a large number of functionalized osteogenic cells is necessary. Therefore, it is strongly recommended to develop strategies to produce sufficient numbers of well-differentiated osteogenic cells from the MSCs. In general, differentiation media with growth factors have been used to facilitate cell differentiation. In the present study, the poly (lactic-co-glycolic acid) (PLGA) nanoparticles incorporating the growth factors were included in the media, resulting in releasing growth factors (dexamethasone and β-glycerophosphate) in the media in the controlled manner. Stable growth and early differentiation of osteogenic cells were achieved by the PLGA-based growth factor releasing system. Moreover, low intensity pulsed ultrasound was applied to this system to induce cell differentiation process. The results revealed that, as a biomarker at early stage of osteogenic cell differentiation, Lamin A/C nuclear protein was efficiently expressed in the cells growing in the presence of PLGA-based growth factor reservoirs and ultrasound. In conclusion, our results showed that the ultrasound stimulation combined with polymeric nanoparticles releasing growth factors could potentially induce osteogenic cell differentiation.

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“…According to previous studies, several factors contribute to promote bone formation and suppress bone resorption ( 34 – 36 ). In the present study, experiments were not designed that were relevant to investigate the crosstalk among miR-338-3p or PCSK5.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

Tong

Zhang²,

et al. 2020

Mol Med Rep

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Bone loss is a disease that is highly associated with aging. This deleterious health condition has become a public concern worldwide, and there is an urgent need to discover more novel therapeutic strategies for the development of age-associated osteoporosis. The present study aimed to explore the association between proprotein convertase subtilisin/kexin type 5 (PCSK5) and microRNA(miR)-338-3p in bone-formation and bone-loss processes. Western blotting assay and reverse transcription-quantitative PCR were employed to analyze PCSK5 and miR-338-3p expression levels in bone mesenchymal stem cells (BMSCs). Dual-luciferase reporter and RNA pull-down assays were used to determine the target. For osteoblastic differentiation verification, alkaline phosphatase activity, osteocalcin secretion detection, bone formation-related indicators (osterix, runt-related gene 2, osteopontin and bone sialoprotein), hematoxylin and eosin staining and Alizarin Red S staining were performed. The findings of the present study indicated that the expression level of PCSK5 was higher in BMSCs from young rat samples, whereas the expression level of miR-338-3p was higher in BMSCs from samples of old rats. Experimental results also revealed that unlike miR-338-3p, downregulation of PCSK5 inhibited osteoblastic differentiation and osteogenesis by inhibiting alkaline phosphatase, osteocalcin, osterix, runt-related transcription factor 2, osteopontin, bone sialoprotein and mineralized nodule formation. Overall, the results suggested that miR-338-3p could suppress age-associated osteoporosis by regulating PCSK5.

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Crucial Role of Lamin A/C in the Migration and Differentiation of MSCs in Bone

Cited by 37 publications

References 189 publications

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

Intracellular and Extracellular Markers of Lethality in Osteogenesis Imperfecta: A Quantitative Proteomic Approach

Synergistic Effect of Growth Factor Releasing Polymeric Nanoparticles and Ultrasound Stimulation on Osteogenic Differentiation

MicroRNA‑338‑3p regulates age‑associated osteoporosis via targeting PCSK5

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