PMID- 36754901
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20230327
IS  - 1432-0827 (Electronic)
IS  - 0171-967X (Print)
IS  - 0171-967X (Linking)
VI  - 112
IP  - 4
DP  - 2023 Apr
TI  - Rescue of High Glucose Impairment of Cultured Human Osteoblasts Using Cinacalcet 
      and Parathyroid Hormone.
PG  - 452-462
LID - 10.1007/s00223-023-01062-7 [doi]
AB  - Patients with type 2 diabetes mellitus (T2DM) experience a higher risk of 
      fractures despite paradoxically exhibiting normal to high bone mineral density 
      (BMD). This has drawn into question the applicability to T2DM of conventional 
      fracture reduction treatments that aim to retain BMD. In a primary human 
      osteoblast culture system, high glucose levels (25 mM) impaired cell 
      proliferation and matrix mineralization compared to physiological glucose levels 
      (5 mM). Treatment with parathyroid hormone (PTH, 10 nM), a bone anabolic agent, 
      and cinacalcet (CN, 1 microM), a calcimimetic able to target the Ca(2+)-sensing 
      receptor (CaSR), were tested for their effects on proliferation and 
      differentiation. Strikingly, CN+PTH co-treatment was shown to promote cell growth 
      and matrix mineralization under both physiological and high glucose conditions. 
      CN+PTH reduced apoptosis by 0.9-fold/0.4-fold as measured by Caspase-3 activity 
      assay, increased alkaline phosphatase (ALP) expression by 1.5-fold/twofold, 
      increased the ratio of nuclear factor kappa-B ligand (RANKL) to osteoprotegerin (OPG) 
      by 2.1-fold/1.6-fold, and increased CaSR expression by 1.7-fold/4.6-fold 
      (physiological glucose/high glucose). Collectively, these findings indicate a 
      potential for CN+PTH combination therapy as a method to ameliorate the negative 
      impact of chronic high blood glucose on bone remodeling.
CI  - (c) 2023. The Author(s).
FAU - Shahen, V A
AU  - Shahen VA
AD  - School of Medical Sciences, Faculty of Medicine and Health, The University of 
      Sydney, Sydney, NSW, 2006, Australia.
FAU - Schindeler, A
AU  - Schindeler A
AD  - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, 
      Sydney, NSW, 2006, Australia.
AD  - Bioengineering & Molecular Medicine Laboratory, The Children's Hospital at 
      Westmead and the, Westmead Institute for Medical Research, Westmead, NSW, 2006, 
      Australia.
FAU - Rybchyn, M S
AU  - Rybchyn MS
AD  - School of Chemical Engineering, University of New South Wales, Sydney, NSW, 2033, 
      Australia.
FAU - Girgis, C M
AU  - Girgis CM
AD  - Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, 
      Sydney, NSW, 2006, Australia.
AD  - Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, Australia.
AD  - Department of Endocrinology, Royal North Shore Hospital, Sydney, Australia.
FAU - Mulholland, B
AU  - Mulholland B
AD  - Graduate School of Medicine, Faculty of Science, Medicine and Health, University 
      of Wollongong, Wollongong, Australia.
AD  - Susan Wakil School of Nursing and Midwifery, Faculty of Medicine and Health, 
      University of Sydney, Sydney, Australia.
FAU - Mason, R S
AU  - Mason RS
AD  - School of Life and Environmental Sciences, Faculty of Science, University of 
      Sydney, Sydney, NSW, 2006, Australia.
FAU - Levinger, I
AU  - Levinger I
AD  - Institute for Health and Sport (IHES), Victoria University, Melbourne, VIC, 
      Australia.
AD  - Australian Institute for Musculoskeletal Science (AIMSS), University of Melbourne 
      and Western Health, St Albans, VIC, Australia.
FAU - Brennan-Speranza, T C
AU  - Brennan-Speranza TC
AUID- ORCID: 0000-0001-5472-4969
AD  - School of Medical Sciences, Faculty of Medicine and Health, The University of 
      Sydney, Sydney, NSW, 2006, Australia. tara.speranza@sydney.edu.au.
AD  - School of Public Health, Faculty of Medicine and Health, The University of 
      Sydney, Sydney, NSW, 2006, Australia. tara.speranza@sydney.edu.au.
LA  - eng
PT  - Journal Article
DEP - 20230208
PL  - United States
TA  - Calcif Tissue Int
JT  - Calcified tissue international
JID - 7905481
RN  - 0 (Parathyroid Hormone)
RN  - UAZ6V7728S (Cinacalcet)
RN  - 0 (Osteoprotegerin)
RN  - IY9XDZ35W2 (Glucose)
RN  - 0 (RANK Ligand)
SB  - IM
MH  - Humans
MH  - *Parathyroid Hormone
MH  - Cinacalcet/pharmacology/metabolism
MH  - *Diabetes Mellitus, Type 2/metabolism
MH  - Osteoblasts/metabolism
MH  - Osteoprotegerin/metabolism
MH  - Glucose/metabolism
MH  - RANK Ligand/metabolism
MH  - Cells, Cultured
PMC - PMC10025212
OTO - NOTNLM
OT  - Cinacalcet
OT  - Diabetes
OT  - Osteoblasts
OT  - PTH
OT  - Parathyroid hormone
COIS- All authors have no conflicts of interest.
EDAT- 2023/02/09 06:00
MHDA- 2023/03/22 06:00
PMCR- 2023/02/08
CRDT- 2023/02/08 23:15
PHST- 2022/09/11 00:00 [received]
PHST- 2023/01/16 00:00 [accepted]
PHST- 2023/02/09 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2023/02/08 23:15 [entrez]
PHST- 2023/02/08 00:00 [pmc-release]
AID - 10.1007/s00223-023-01062-7 [pii]
AID - 1062 [pii]
AID - 10.1007/s00223-023-01062-7 [doi]
PST - ppublish
SO  - Calcif Tissue Int. 2023 Apr;112(4):452-462. doi: 10.1007/s00223-023-01062-7. Epub 
      2023 Feb 8.