Annexin Animal Models—From Fundamental Principles to Translational Research

Grewal, Thomas; Rentero, Carles; Enrich, Carlos; Wahba, Mohamed; Raabe, Carsten A.; Rescher, Ursula

doi:10.3390/ijms22073439

Cited by 33 publications

(33 citation statements)

References 442 publications

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“…We hypothesize that annexins could participate in the osteogenic inductive properties of OM-dECM derived from DPSCs. A positive role of annexins on osteogenic differentiation and ossification has been reported (Grewal et al, 2021). ANXA1, ANXA4, ANXA5, ANXA6, ANXA7, and ANXA11 were enriched in OM-ECM compared to N-ECM in the present study.…”

Section: Discussionsupporting

confidence: 75%

Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization

Nowwarote

Petit

Ferre

et al. 2022

Front. Bioeng. Biotechnol.

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Background: Extracellular matrix (ECM) plays a pivotal role in many physiological processes. ECM macromolecules and associated factors differ according to tissues, impact cell differentiation, and tissue homeostasis. Dental pulp ECM may differ from other oral tissues and impact mineralization. Thus, the present study aimed to identify the matrisome of ECM proteins derived from human dental pulp stem cells (DPSCs) and its ability to regulate mineralization even in cells which do not respond to assaults by mineralization, the human gingival fibroblasts (GF).Methods: ECM were extracted from DPSCs cultured in normal growth medium supplemented with L-ascorbic acid (N-ECM) or in osteogenic induction medium (OM-ECM). ECM decellularization (dECM) was performed using 0.5% triton X-100 in 20 mM ammonium hydroxide after 21 days. Mass spectrometry and proteomic analysis identified and quantified matrisome proteins.Results: The dECM contained ECM proteins but lacked cellular components and mineralization. Interestingly, collagens (COL6A1, COL6A2, and COL6A3) and elastic fibers (FBN1, FBLN2, FN1, and HSPG2) were significantly represented in N-ECM, while annexins (ANXA1, ANXA4, ANXA5, ANXA6, ANXA7, and ANXA11) were significantly overdetected in OM-ECM. GF were reseeded on N-dECM and OM-dECM and cultured in normal or osteogenic medium. GF were able to attach and proliferate on N-dECM and OM-dECM. Both dECM enhanced mineralization of GF at day 14 compared to tissue culture plate (TCP). In addition, OM-dECM promoted higher mineralization of GF than N-dECM although cultured in growth medium.Conclusions: ECM derived from DPSCs proved to be osteoinductive, and this knowledge supported cell-derived ECM can be further utilized for tissue engineering of mineralized tissues.

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Section: Discussionsupporting

confidence: 75%

Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization

Nowwarote

Petit

Ferre

et al. 2022

Front. Bioeng. Biotechnol.

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“…In fact, most annexin functions in cells are due to their dynamic and reversible binding to membranes (Gerke et al, 2005;Enrich et al, 2017). More recently, mouse models lacking individual annexins validated proposed functions in complex physiological processes in vivo (Alvarez-Guaita et al, 2020;Grewal et al, 2021). Annexins are present in multiple cellular compartments to regulate numerous functions, including membrane trafficking, cytoskeleton dynamics, ion channels, cell signalling, membrane repair and pro-or antiinflammatory activities.…”

Section: Annexins-novel Players In Intracellular Communication and Membrane Contact Sitesmentioning

confidence: 99%

“…AnxA1 is ubiquitously expressed and found at the plasma membrane, endo-/exocytic vesicles, the cytoskeleton and nucleus ( Grewal et al, 2021 ). Moreover, AnxA1 acts as a tether connecting the ER and MVBs ( Eden et al, 2010 ; Eden et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…AnxA6 has recently also been associated with MCS formation ( Meneses-Salas et al, 2020b ). Further to its association with the plasma membrane, endo-/exocytic vesicles, mitochondria and lipid droplets ( Grewal et al, 2021 ), AnxA6 was additionally detected in MAMs ( Sala-Vila et al, 2016 ), specialized membrane subdomains enriched in cholesterol and neutral lipids that permit the communication between the ER and mitochondria ( Vance, 1990 ; Hayashi and Su, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

“…Recently, AnxA11 was detected in lysosomes that connect with RNA granules ( Liao et al, 2019 ). Alike AnxA1 and A6, AnxA11 is widely expressed with diverse, often Ca 2+ - and S100A6 (calcyclin)-dependent functions in cytoplasmic and nuclear membrane locations, relevant for growth, cell cycle progression, differentiation, and exocytosis ( Grewal et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation

Enrich

Tebar

et al. 2022

Front. Cell Dev. Biol.

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Membrane contact sites (MCS) are specialized small areas of close apposition between two different organelles that have led researchers to reconsider the dogma of intercellular communication via vesicular trafficking. The latter is now being challenged by the discovery of lipid and ion transfer across MCS connecting adjacent organelles. These findings gave rise to a new concept that implicates cell compartments not to function as individual and isolated entities, but as a dynamic and regulated ensemble facilitating the trafficking of lipids, including cholesterol, and ions. Hence, MCS are now envisaged as metabolic platforms, crucial for cellular homeostasis. In this context, well-known as well as novel proteins were ascribed functions such as tethers, transporters, and scaffolds in MCS, or transient MCS companions with yet unknown functions. Intriguingly, we and others uncovered metabolic alterations in cell-based disease models that perturbed MCS size and numbers between coupled organelles such as endolysosomes, the endoplasmic reticulum, mitochondria, or lipid droplets. On the other hand, overexpression or deficiency of certain proteins in this narrow 10–30 nm membrane contact zone can enable MCS formation to either rescue compromised MCS function, or in certain disease settings trigger undesired metabolite transport. In this “Mini Review” we summarize recent findings regarding a subset of annexins and discuss their multiple roles to regulate MCS dynamics and functioning. Their contribution to novel pathways related to MCS biology will provide new insights relevant for a number of human diseases and offer opportunities to design innovative treatments in the future.

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Annexin A1, A2, A5, and A6 involvement in human pathologies

et al. 2023

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The human genome codes for 12 annexins with highly homologous membrane‐binding cores and unique amino termini, which endow each protein with its specific biological properties. Not unique to vertebrate biology, multiple annexin orthologs are present in almost all eukaryotes. Their ability to combine either dynamically or constitutively with membrane lipid bilayers is hypothetically the key property that has led to their retention and multiple adaptation in eukaryotic molecular cell biology. Annexin genes are differentially expressed in many cell types but their disparate functions are still being discovered after more than 40 years of international research. A picture is emerging from gene knock down and knock out studies of individual annexins that these are important supporters rather than critical players in organism development and normal cell and tissue function. However, they appear to be highly significant “early responders” toward challenges arising from cell and tissue abiotic or biotic stress. In humans, recent focus has been on involvement of the annexin family for its involvement in diverse pathologies, especially cancer. From what has become an exceedingly broad field of investigation, we have selected four annexins in particular: AnxA1, 2, 5, and 6. Present both within and external to cells, these annexins are currently under intensive investigation in translational research as biomarkers of cellular dysfunction and as potential therapeutic targets for inflammatory conditions, neoplasia, and tissue repair. Annexin expression and release in response to biotic stress appears to be a balancing act. Under‐ or over‐expression in different circumstances appears to damage rather than restore a healthy homeostasis. This review reflects briefly on what is already known of the structures and molecular cell biology of these selected annexins and considers their actual and potential roles in human health and disease.

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Annexin Animal Models—From Fundamental Principles to Translational Research

Cited by 33 publications

References 442 publications

Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization

Extracellular Matrix Derived From Dental Pulp Stem Cells Promotes Mineralization

Annexins Bridging the Gap: Novel Roles in Membrane Contact Site Formation

Annexin A1, A2, A5, and A6 involvement in human pathologies

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