AZADEH MONTASERI

Dottoressa di ricerca

ciclo: XXXVI


supervisore: Prof. Antonio Filippini

Titolo della tesi: Uncovering the impact of endolysosomal Two-pore channel 2 (TPC2) on the autophagy pathway during osteoblastogenesis and osteoclastogenesis

Rational: Endo-lysosomal two-pore channels 2 (TPC2) are voltage-gated ion channels with distinct ion selectivity as are regulated by both NAADP and PI (3,5)P2 that control the release of Ca2+ and Na+, respectively. As the lysosomal function is fundamental for regulation of different aspects of the autophagy flux, TPC2 channels are also associated with control of autophagy. Interestingly, autophagy has an important role in regulation of bone cells differentiation and function. General objectives: This study aimed to give thorough insight to the interaction between TPC2 and the autophagy pathway in the control of osteoblast and osteoclast differentiation and function. Experimental design and methods: To achieve the purposes of this project, mesenchymal stem cells (MSCs) and human osteosarcoma cells (SAOS-2) were used to assess osteoblastogenesis and bone mineralization, respectively, while the peripheral blood mononuclear cells (PBMCs) have been used to study osteoclastogenesis. The cells have been treated with different pharmacological TPC2 inhibitors including naringenin, tetrandrine, MT-8 and SG-094 during their differentiation process. At the end, formation of osteoblasts and in vitro bone mineralization were evaluated by alkaline phosphatase, alizarin red S and Von Kossa staining methods, while the formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) and phalloidin staining methods. Western blot analysis was done to investigate the expression of osteoblast and osteoclast specific markers and autophagy-related molecules. Results: The inhibition of TPC2 activity stimulated osteoblast differentiation from MSCs as confirmed by alkaline phosphatase staining and western blot analysis for RUNX2 expression. Moreover, inhibition of TPC2 activity increased the bone mineralization by osteoblast-like (SAOS-2) cells. Interestingly, TPC2 inhibition in osteoblast and SAOS-2 cells resulted in reduced expression of p62 and LC3II/I while the expression of mammalian target of rapamycin complex 1 (mTORC1) as the master regulator of autophagy that negatively controls this pathway was increased; this, together with increased RUNX2 indicates promoted osteoblast differentiation. Furthermore, TPC2 inhibition showed a bi-phasic effects on osteoclastogenesis: formation of giant and multinuclear osteoclasts with evident F-actin ring was induced by TPC2 inhibitors at lower concentrations, while decreased osteoclast formation was observed in response to naringenin and MT-8 at high concentrations. Likewise, TPC2 inhibition downregulated the expression of LC3II/I and p62 and increased expression of mTORC1. Interestingly, inhibition of mTORC1 activity by rapamycin as an autophagy enhancer reversed the osteoclast differentiation induced by TPC2 inhibitors. Conclusion: Inhibition of TPC2 channel activity can increase osteoblast differentiation and bone mineralization and inhibits the completion of the autophagic flux. Enhanced expression of RUNX2/mTORC1 could be the reason for increased osteoblastogenesis due to TPC2 inhibition. Furthermore, low doses of TPC2 inhibitors stimulated osteoclast formation and blocked the autophagy flux termination by targeting mTORC1 and rapamycin opposed their stimulatory effects.

Produzione scientifica

11573/1669745 - 2023 - Extracellular vesicles of immune cells; immunomodulatory impacts and therapeutic potentials
Mahmoudi, Fariba; Hanachi, Parichehr; Montaseri, Azadeh - 01g Articolo di rassegna (Review)
rivista: CLINICAL IMMUNOLOGY (New York, NY: Elsevier Science Amsterdam: Elsevier Orlando FL: Academic Press, c1999-) pp. 1-9 - issn: 1521-6616 - wos: WOS:000939380900001 (8) - scopus: 2-s2.0-85147912057 (9)

11573/1463717 - 2020 - The role of autophagy in osteoclast differentiation and bone resorption function
Montaseri, A.; Giampietri, C.; Rossi, M.; Riccioli, A.; Fattore, A. D.; Filippini, A. - 01g Articolo di rassegna (Review)
rivista: BIOMOLECULES (Basel: MDPI) pp. 1-16 - issn: 2218-273X - wos: WOS:000584139800001 (47) - scopus: 2-s2.0-85091873742 (56)

11573/1560123 - 2020 - Preparation and characterization of novel anti-inflammatory biological agents based on piroxicam-loaded poly-ε-caprolactone nano-particles for sustained NSAID delivery
Rahmani Del Bakhshayesh, A.; Akbarzadeh, A.; Alihemmati, A.; Tayefi Nasrabadi, H.; Montaseri, A.; Davaran, S.; Abedelahi, A. - 01a Articolo in rivista
rivista: DRUG DELIVERY (Orlando, FL : Academic Press, c1993- Taylor & Francis Limited:Rankine Road, Basingstoke RG24 8PR United Kingdom:011 44 1256 813035, EMAIL: madeline.sims@tandf.co.uk, info@tandf.co.uk, INTERNET: http://www.tandf.co.uk, Fax: 011 44 1256 330245) pp. 269-282 - issn: 1071-7544 - wos: WOS:000510551100001 (19) - scopus: 2-s2.0-85079214911 (22)

11573/1558816 - 2020 - Differential biological behavior of fibroblasts and endothelial cells under aloe vera gel culturing
Shafaie, S; Andalib, S; Shafaei, H; Montaseri, A; Tavakolizadeh, M - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE () pp. 234-245 - issn: 2251-9637 - wos: WOS:000605927800007 (10) - scopus: 2-s2.0-85100134542 (13)

11573/1559729 - 2019 - An overview of advanced biocompatible and biomimetic materials for creation of replacement structures in the musculoskeletal systems: focusing on cartilage tissue engineering
Del Bakhshayesh, A. R.; Asadi, N.; Alihemmati, A.; Tayefi Nasrabadi, H.; Montaseri, A.; Davaran, S.; Saghati, S.; Akbarzadeh, A.; Abedelahi, A. - 01g Articolo di rassegna (Review)
rivista: JOURNAL OF BIOLOGICAL ENGINEERING (London : BioMed Central) pp. - - issn: 1754-1611 - wos: WOS:000497754800002 (68) - scopus: 2-s2.0-85075284453 (88)

11573/1560357 - 2019 - Biological effects of resin monomers on oral cell populations: descriptive analysis of literature
Pagano, S.; Coniglio, M.; Valenti, C.; Negri, P.; Lombardo, G.; Costanzi, E.; Cianetti, S.; Montaseri, A.; Marinucci, L. - 01a Articolo in rivista
rivista: EUROPEAN JOURNAL OF PAEDIATRIC DENTISTRY (Carimate: Ariesdue.) pp. 224-232 - issn: 1591-996X - wos: WOS:000493453100010 (27) - scopus: 2-s2.0-85071772994 (29)

11573/1559911 - 2019 - Cytotoxicity of universal dental adhesive systems: assessment in vitro assays on human gingival fibroblasts
Pagano, S.; Lombardo, G.; Balloni, S.; Bodo, M.; Cianetti, S.; Barbati, A.; Montaseri, A.; Marinucci, L. - 01a Articolo in rivista
rivista: TOXICOLOGY IN VITRO (Attuale: -OXFORD, ENGLAND: PERGAMON-ELSEVIER SCIENCE LTD Precedente: -Oxford; New York: Pergamon.) pp. 252-260 - issn: 0887-2333 - wos: WOS:000486105900028 (37) - scopus: 2-s2.0-85067237089 (36)

11573/1560127 - 2019 - Quercetin alleviates high glucose-induced damage on human umbilical vein endothelial cells by promoting autophagy
Rezabakhsh, A.; Rahbarghazi, R.; Malekinejad, H.; Fathi, F.; Montaseri, A.; Garjani, A. - 01a Articolo in rivista
rivista: PHYTOMEDICINE (-Jena,Germany: Elsevier -Jena,Germany: Urban & Fischer Verlag Jena) pp. 183-193 - issn: 0944-7113 - wos: WOS:000463528800021 (61) - scopus: 2-s2.0-85056623004 (70)

11573/1558941 - 2018 - Recent advances on biomedical applications of scaffolds in wound healing and dermal tissue engineering
Del Bakhshayesh, Ar; Annabi, N; Khalilov, R; Akbarzadeh, A; Samiei, M; Alizadeh, E; Alizadeh-Ghodsi, M; Davaran, S; Montaseri, A - 01a Articolo in rivista
rivista: ARTIFICIAL CELLS, NANOMEDICINE, AND BIOTECHNOLOGY (Abingdon, Oxfordshire, United Kingdom] : Taylor & Francis London: Informa Healthcare, [2013]-) pp. 691-705 - issn: 2169-1401 - wos: WOS:000428093600005 (149) - scopus: 2-s2.0-85044203777 (184)

11573/1560129 - 2018 - Mummy material can promote differentiation of adipose derived stem cells into osteoblast through enhancement of bone specific transcription factors expression
Eyvazi, M.; Farahzadi, R.; Fathi, N. K.; Karimipour, M.; Rad, J. S.; Montaseri, A. - 01a Articolo in rivista
rivista: ADVANCED PHARMACEUTICAL BULLETIN (Tabriz: Tabriz University of Medical Sciences, Faculty of Pharmacy, 2011) pp. 457-464 - issn: 2228-5881 - wos: WOS:000473817900012 (2) - scopus: 2-s2.0-85052588636 (1)

11573/1560141 - 2018 - Mummy prevents IL-1β-Induced inflammatory responses and cartilage matrix degradation via inhibition of NF-κB subunits gene expression in pellet culture system
Morrovati, F.; Fathi, N. K.; Rad, J. S.; Montaseri, A. - 01a Articolo in rivista
rivista: ADVANCED PHARMACEUTICAL BULLETIN (Tabriz: Tabriz University of Medical Sciences, Faculty of Pharmacy, 2011) pp. 283-289 - issn: 2228-5881 - wos: WOS:000438865100013 (8) - scopus: 2-s2.0-85048854686 (7)

11573/1560125 - 2018 - Silibinin protects human endothelial cells from high glucose-induced injury by enhancing autophagic response
Rezabakhsh, A.; Fathi, F.; Bagheri, H. S.; Malekinejad, H.; Montaseri, A.; Rahbarghazi, R.; Garjani, A. - 01a Articolo in rivista
rivista: JOURNAL OF CELLULAR BIOCHEMISTRY (John Wiley & Sons Incorporated:Customer Service, 111 River Street:Hoboken, NJ 07030:(800)225-5945, (201)748-6000, EMAIL: societyinfo@wiley.com, INTERNET: http://www.wiley.com, Fax: (212)748-6551) pp. 8084-8094 - issn: 0730-2312 - wos: WOS:000447201500017 (36) - scopus: 2-s2.0-85054701050 (41)

11573/1560131 - 2018 - Synthesis and in vitro evaluation of thermosensitive hydrogel scaffolds based on (PNIPAAm-PCL-PEG-PCL-PNIPAAm)/Gelatin and (PCL-PEG-PCL)/Gelatin for use in cartilage tissue engineering
Saghebasl, S.; Davaran, S.; Rahbarghazi, R.; Montaseri, A.; Salehi, R.; Ramazani, A. - 01a Articolo in rivista
rivista: JOURNAL OF BIOMATERIALS SCIENCE POLYMER EDITION (VSP International Science Publishers:Godfried van Seystlaan 47, 3703 BR Zeist Netherlands:011 31 30 6925790, EMAIL: vsppub@compuserve.com, INTERNET: http://www.vsppub.com, Fax: 011 31 30 6932081) pp. 1185-1206 - issn: 0920-5063 - wos: WOS:000428861200006 (58) - scopus: 2-s2.0-85042916354 (69)

11573/1560286 - 2017 - Conditioned medium of Wharton's jelly derived stem cells can enhance the cartilage specific genes expression by chondrocytes in monolayer and mass culture systems
Famian, M. H.; Saheb, S. M.; Montaseri, A. - 01a Articolo in rivista
rivista: ADVANCED PHARMACEUTICAL BULLETIN (Tabriz: Tabriz University of Medical Sciences, Faculty of Pharmacy, 2011) pp. 123-130 - issn: 2228-5881 - wos: WOS:000401835400016 (23) - scopus: 2-s2.0-85017548165 (23)

11573/1560281 - 2017 - Rapamycin inhibits oxidative/nitrosative stress and enhances angiogenesis in high glucose-treated human umbilical vein endothelial cells: role of autophagy
Rezabakhsh, A.; Ahmadi, M.; Khaksar, M.; Montaseri, A.; Malekinejad, H.; Rahbarghazi, R.; Garjani, A. - 01a Articolo in rivista
rivista: BIOMÉDECINE & PHARMACOTHÉRAPIE (Paris: Editions Scientifique & Medical Elsevier) pp. 885-894 - issn: 0753-3322 - wos: WOS:000407923000096 (54) - scopus: 2-s2.0-85023619973 (56)

11573/1560135 - 2017 - Effect of hydroxychloroquine on oxidative/nitrosative status and angiogenesis in endothelial cells under high glucose condition
Rezabakhsh, A.; Montazersaheb, S.; Nabat, E.; Hassanpour, M.; Montaseri, A.; Malekinejad, H.; Movassaghpour, A. A.; Rahbarghazi, R.; Garjani, A. - 01a Articolo in rivista
rivista: BIOIMPACTS (Tabriz: Tabriz University of Medical Sciences, 2011) pp. 219-226 - issn: 2228-5660 - wos: WOS:000423937100003 (21) - scopus: 2-s2.0-85040964888 (23)

11573/1560321 - 2016 - Effects of continuous wave and fractionated diode laser on human fibroblast cancer and dermal normal cells by zinc phthalocyanine in photodynamic therapy: a comparative study
Navaeipour, F.; Afsharan, H.; Tajalli, H.; Mollabashi, M.; Ranjbari, F.; Montaseri, A.; Rashidi, M. -R. - 01a Articolo in rivista
rivista: JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY (Lausanne : Elsevier Sequoia) pp. 456-462 - issn: 1011-1344 - wos: WOS:000381653800054 (12) - scopus: 2-s2.0-84975148047 (15)

11573/1560143 - 2016 - Impact of prunus cerasus on PGR and HAS2 in cumulus cells and fertility outcome
Vansofla, F. N.; Roshangar, L.; Montaseri, A.; Rad, J. S. - 01a Articolo in rivista
rivista: ADVANCED PHARMACEUTICAL BULLETIN (Tabriz: Tabriz University of Medical Sciences, Faculty of Pharmacy, 2011) pp. 65-69 - issn: 2228-5881 - wos: WOS:000379778300010 (6) - scopus: 2-s2.0-84962464475 (6)

11573/1560292 - 2015 - Evaluation of the melatonin and oxidative stress markers level in serum of fertile and infertile women
Rad, Ss; Abbasalizadeh, S; Haghjo, Ag; Sadagheyani, M; Montaseri, A; Rad, Js - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF REPRODUCTIVE BIOMEDICINE (Yazd : Shahid Sadoughi University of Medical Sciences and Health Services) pp. 439-444 - issn: 2476-4108 - wos: WOS:000375573200008 (10) - scopus: 2-s2.0-84941331991 (13)

11573/1560300 - 2013 - Serum Levels of Melatonin and Oxidative Stress Markers and Correlation between Them in Infertile Men
Soleimani Rad, Sara; Abbasalizadeh, Shamsi; Ghorbani Haghjo, Amir; Sadagheyani, Mehzad; Montaseri, Azadeh; Soleimani Rad, Jafar - 01a Articolo in rivista
rivista: Journal of caring sciences (Professor L. Valizadeh) pp. 287-94- - issn: - wos: (0) - scopus: (0)

11573/1560328 - 2011 - Curcumin modulates nuclear factor κB (nf-κB)-mediated inflammation in human tenocytes in vitro: Role of the phosphatidylinositol 3-kinase/Akt pathway
Buhrmann, C.; Mobasheri, A.; Busch, F.; Aldinger, C.; Stahlmann, R.; Montaseri, A.; Shakibaei, M. - 01a Articolo in rivista
rivista: THE JOURNAL OF BIOLOGICAL CHEMISTRY (American Society for Biochemistry and Molecular Biology:9650 Rockville Pike:Bethesda, MD 20814:(301)530-7145, EMAIL: asbmb@asbmb.faseb.org, INTERNET: http://www.faseb.org/asbmb, Fax: (301)571-1824) pp. 28556-28566 - issn: 0021-9258 - wos: WOS:000293557800070 (181) - scopus: 2-s2.0-80051484401 (211)

11573/1560311 - 2011 - Study of Foeniculum vulgare Effect on Folliculogenesis in Female Mice
Khazaei, M; Montaseri, A; Khazaei, Mr; Khanahmadi, M - 01a Articolo in rivista
rivista: INTERNATIONAL JOURNAL OF FERTILITY AND STERILITY (Tehran: Royan Institute,) pp. 122-127 - issn: 2008-076X - wos: WOS:000300134900001 (37) - scopus: 2-s2.0-84855889970 (45)

11573/1560352 - 2011 - IGF-1 and PDGF-bb suppress IL-1β-induced cartilage degradation through down-regulation of NF-κB signaling: Involvement of Src/PI-3k/AKT pathway
Montaseri, A.; Busch, F.; Mobasheri, A.; Buhrmann, C.; Aldinger, C.; Rad, J. S.; Shakibaei, M. - 01a Articolo in rivista
rivista: PLOS ONE (San Francisco, CA : Public Library of Science) pp. e28663- - issn: 1932-6203 - wos: WOS:000298369100073 (173) - scopus: 2-s2.0-83355173227 (183)

11573/1560348 - 2010 - Recurrent Intracranial Haemangiopericytoma compatible to Synovial Sarcoma
Aleagha, Me; Montaseri, A; Tahmasian, M; Shobiri, E; Torbaghan, Ss - 01a Articolo in rivista
rivista: JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION (Karachi: Pakistan Medical Association.) pp. 586-588 - issn: 0030-9982 - wos: WOS:000278781900021 (0) - scopus: 2-s2.0-77954526397 (0)

11573/1560339 - 2009 - Letrozole stimulates the growth of human endometrial explants cultured in three-dimensional fibrin matrix
Khazaei, M.; Montaseri, A.; Casper, R. F. - 01a Articolo in rivista
rivista: FERTILITY AND STERILITY (Usa: Elsevier -Highway, Birmingham, AL: American Society for Reproductive Medicine) pp. 2172-2176 - issn: 0015-0282 - wos: WOS:000265969300028 (17) - scopus: 2-s2.0-65049090789 (18)

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