PMID- 35956385
OWN - NLM
STAT- MEDLINE
DCOM- 20220815
LR  - 20220824
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 14
IP  - 15
DP  - 2022 Aug 5
TI  - Estrogen Receptor 1 (ESR1) and the Wnt/beta-Catenin Pathway Mediate the Effect of 
      the Coumarin Derivative Umbelliferon on Bone Mineralization.
LID - 10.3390/nu14153209 [doi]
LID - 3209
AB  - Bone physiology is regulated by osteoblast and osteoclast activities, both 
      involved in the bone remodeling process, through deposition and resorption 
      mechanisms, respectively. The imbalance between these two phenomena contributes 
      to the onset of bone diseases. Among these, osteoporosis is the most common 
      metabolic bone disorder. The therapies currently used for its treatment include 
      antiresorptive and anabolic agents associated with side effects. Therefore, 
      alternative therapeutic approaches, including natural molecules such as coumarin 
      and their derivatives, have recently shown positive results. Thus, our proposal 
      was to investigate the effect of the coumarin derivative umbelliferon (UF) using 
      an interesting model of human osteoblasts (hOBs) isolated from osteoporotic 
      patients. UF significantly improved the activity of osteoporotic-patient-derived 
      hOBs via estrogen receptor 1 (ESR1) and the downstream activation of beta-catenin 
      pathway. Additionally, hOBs were co-cultured in microgravity with human 
      osteoclasts (hOCs) using a 3D system bioreactor, able to reproduce the bone 
      remodeling unit in bone loss conditions in vitro. Notably, UF exerted its 
      anabolic role by reducing the multinucleated cells. Overall, our study confirms 
      the potential efficacy of UF in bone health, and identified, for the first time, 
      a prospective alternative natural compound useful to prevent/treat bone loss 
      diseases such as osteoporosis.
FAU - Pelusi, Letizia
AU  - Pelusi L
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Mandatori, Domitilla
AU  - Mandatori D
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Di Pietrantonio, Nadia
AU  - Di Pietrantonio N
AUID- ORCID: 0000-0001-6604-0804
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Del Pizzo, Francesco
AU  - Del Pizzo F
AD  - Department of Neurosciences, Imaging and Clinical Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Di Tomo, Pamela
AU  - Di Tomo P
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Di Pietro, Natalia
AU  - Di Pietro N
AUID- ORCID: 0000-0001-9720-2116
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Buda, Roberto
AU  - Buda R
AUID- ORCID: 0000-0002-8692-0857
AD  - Department of Medicine and Aging Sciences, University "G. D'Annunzio" 
      Chieti-Pescara, 66100 Chieti, Italy.
FAU - Genovese, Salvatore
AU  - Genovese S
AD  - Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Epifano, Francesco
AU  - Epifano F
AUID- ORCID: 0000-0002-0381-7812
AD  - Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Pandolfi, Assunta
AU  - Pandolfi A
AUID- ORCID: 0000-0003-4135-7631
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Fiorito, Serena
AU  - Fiorito S
AD  - Department of Pharmacy, University "G. D'Annunzio" of Chieti-Pescara, 66100 
      Chieti, Italy.
FAU - Pipino, Caterina
AU  - Pipino C
AUID- ORCID: 0000-0002-4350-8686
AD  - Department of Medical, Oral and Biotechnological Sciences, Center for Advanced 
      Studies and Technology-CAST, University G. D'Annunzio of Chieti-Pescara, 66100 
      Chieti, Italy.
LA  - eng
GR  - (grant no. 21, ex 230)/PON-MISE Sustainable Growth Funding-DD 27/09/2018/
PT  - Journal Article
DEP - 20220805
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0 (Coumarins)
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (beta Catenin)
SB  - IM
MH  - *Bone Diseases, Metabolic/metabolism
MH  - *Bone Resorption/drug therapy
MH  - Calcification, Physiologic
MH  - Cell Differentiation
MH  - Coumarins/therapeutic use
MH  - Estrogen Receptor alpha/*metabolism
MH  - Humans
MH  - Osteoblasts
MH  - Osteoclasts
MH  - Osteogenesis
MH  - *Osteoporosis/drug therapy/metabolism
MH  - Prospective Studies
MH  - Wnt Signaling Pathway
MH  - beta Catenin/metabolism
PMC - PMC9370350
OTO - NOTNLM
OT  - 3D culture
OT  - bone mineralization
OT  - coumarin derivatives
OT  - osteoblast
OT  - osteoclast
OT  - osteoporosis
OT  - umbelliferon
COIS- The authors declare no conflict of interest.
EDAT- 2022/08/13 06:00
MHDA- 2022/08/16 06:00
PMCR- 2022/08/05
CRDT- 2022/08/12 01:17
PHST- 2022/07/11 00:00 [received]
PHST- 2022/08/01 00:00 [revised]
PHST- 2022/08/03 00:00 [accepted]
PHST- 2022/08/12 01:17 [entrez]
PHST- 2022/08/13 06:00 [pubmed]
PHST- 2022/08/16 06:00 [medline]
PHST- 2022/08/05 00:00 [pmc-release]
AID - nu14153209 [pii]
AID - nutrients-14-03209 [pii]
AID - 10.3390/nu14153209 [doi]
PST - epublish
SO  - Nutrients. 2022 Aug 5;14(15):3209. doi: 10.3390/nu14153209.