Evidence map›Paper›PMID 42090110›Full record

ArticleJournal of endocrinological investigation2026

Inhibition of endolysosomal two-pore channel 2 (TPC2) induces osteoblast differentiation and matrix mineralization while targeting autophagy.

Azadeh Montaseri, Michela Rossi, Giulia Battafarano, Anna Riccioli, Fioretta Palombi, Claudia Giampietri, Domenico Liguoro, Rita Mancini, Martina Meucci, Biagio Palmisano and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of endocrinological investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Azadeh MontaseriDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy.
Michela RossiBone Physiopathology Research Unit, Translational Pediatrics and Clinical Genetics Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Giulia BattafaranoBone Physiopathology Research Unit, Translational Pediatrics and Clinical Genetics Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.
Anna RiccioliDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy.
Fioretta PalombiDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy.
Claudia GiampietriDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy.
Domenico LiguoroSAFU Laboratory, Department of Research, Advanced Diagnostics and Technological Innovation, Translational Research Area, IRCCS Regina Elena National Cancer Institute, 00144, Rome, Italy.
Rita ManciniDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, "Sapienza" University, 00185, Rome, Italy.
Martina MeucciDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy.
Biagio PalmisanoDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Mara RiminucciDepartment of Molecular Medicine, Sapienza University of Rome, 00161, Rome, Italy.
Marco KellerDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians- University, Munich, Germany.
Franz BracherDepartment of Pharmacy - Center for Drug Research, Ludwig-Maximilians- University, Munich, Germany.
Christian GrimmImmunology, Infection and Pandemic Research IIP, Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Munich, Frankfurt, Germany.
Kaoru UmeharaFaculty of Kampo Pharmacy, Yokohama University of Pharmacy, Matano-Cho, Totsuka-Ward, Yokohama, Kanagawa, Japan.
Wanchai De-EknamkulDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
Antonio FilippiniDepartment of Anatomy, Histology, Forensic Medicine and Orthopaedics, Unit of Histology and Medical Embryology and Unit of Human Anatomy, Sapienza University of Rome, Via A. Scarpa, 16, 00161, Rome, Italy. antonio.filippini@uniroma1.it.ORCID http://orcid.org/0000-0001-8453-287X
Andrea Del FattoreBone Physiopathology Research Unit, Translational Pediatrics and Clinical Genetics Research Division, Bambino Gesù Children's Hospital, IRCCS, 00146, Rome, Italy.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeEndolysosomal two-pore channels (TPCs) are non-selective cation channels that control the release of Ca

methodsPrimary human mesenchymal stem cells (hMSCs) and human osteoblast-like cells (Saos-2) were used to assess osteoblastogenesis and bone mineralization, respectively. MSCs were treated with different pharmacological TPC2 inhibitors including naringenin, tetrandrine, MT-8 and SG-094 during their differentiation process. Finally, formation of osteoblasts and in vitro bone mineralization were evaluated by alkaline phosphatase, alizarin red S and Von Kossa staining. Western blot analysis was performed to investigate the expression of autophagy-related molecules.

resultsThe inhibition of TPC2 activity stimulates osteoblast differentiation from hMSCs and bone mineralization by Saos-2 cells. Interestingly, TPC2 inhibition reduces beclin-1 and LC3-II expression while that of the mammalian target of rapamycin (mTOR), the master regulator of autophagy, increases. Inhibition of mTOR activity by rapamycin reverses osteoblast differentiation induced by TPC2 inhibitor SG-094.

conclusionInhibition of TPC2 channel activity increases osteoblast differentiation and bone mineralization in vitro and interferes with the completion of autophagy, upregulating phosphorylated mTOR.

Indexed as

AutophagyCalcification, PhysiologicCalcium ChannelsCell DifferentiationMesenchymal Stem CellsOsteoblastsCells, CulturedHumansLysosomesOsteogenesisTwo-Pore ChannelsCalcium ChannelsTPCN2 protein, humanTwo-Pore ChannelsAutophagyMineralizationmTOROsteoblastTwo-pore channel 2 (TPC2)

Identifiers

PMID42090110
PMCPMC13498500

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.