PMID- 28507207
OWN - NLM
STAT- MEDLINE
DCOM- 20170911
LR  - 20201209
IS  - 1479-6805 (Electronic)
IS  - 0022-0795 (Linking)
VI  - 233
IP  - 3
DP  - 2017 Jun
TI  - Role of osteocytes in mediating bone mineralization during hyperhomocysteinemia.
PG  - 243-255
LID - 10.1530/JOE-16-0562 [doi]
AB  - Hyperhomocysteinemia (HHCY) is a risk factor for osteoporosis but whether HHCY 
      affects bone mineralization or not is still ambiguous. Herein we evaluated 
      whether homocysteine affects tissue mineral density (TMD) of cortical bone and if 
      so the role of osteocytes. CD1 mice administered with homocysteine (5 mg/100 g 
      body weight, i.p.) for 7, 15 and 30 days showed temporal changes in TMD and 
      osteocyte lacunar density in femoral cortices. Short-term administration of 
      homocysteine (day 7) increased osteocyte lacunar density and reduced TMD 
      evidenced by microCT50 while prolonged administration of homocysteine (day 30) 
      reinstated TMD and lacunar density to baseline values. Major differences were 
      decreased number of nucleated osteocyte lacunae, increased number of empty 
      lacunae and cleaved caspase 3-positive osteocyte lacunae in day 30 HHCY bone 
      evidenced by H&E staining and immunohistochemistry. Other differences were 
      induction in mineralization genes like Dmp1, Phex and Sost in cortical bone by 
      real-time PCR and increased number of Dmp1- and Sost-positive osteocyte lacunae 
      in day 30 HHCY bone evidenced by immunohistochemistry. Both HHCY day 7 and day 30 
      samples showed reduced Young's modulus demonstrating that biomechanical property 
      of bone was lost during early HHCY itself, which did not improve with recovery of 
      TMD. Our results thus demonstrate occurrence of two phases in cortical bone upon 
      HHCY: the early phase that involved loss of TMD and increase in osteocyte numbers 
      and a late phase that involved osteocyte reprogramming, apoptosis and 
      mineralization, which reinstated TMD but compromised biomechanical property. To 
      conclude, osteocytes have a potential role in arbitrating bone pathogenesis 
      during HHCY.
CI  - (c) 2017 Society for Endocrinology.
FAU - Vijayan, Viji
AU  - Vijayan V
AD  - Molecular Sciences LaboratoryNational Institute of Immunology, New Delhi, India 
      vijivijayan@nii.ac.in sarika@nii.ac.in.
FAU - Gupta, Sarika
AU  - Gupta S
AD  - Molecular Sciences LaboratoryNational Institute of Immunology, New Delhi, India 
      vijivijayan@nii.ac.in sarika@nii.ac.in.
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Endocrinol
JT  - The Journal of endocrinology
JID - 0375363
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Biomarkers)
RN  - 0 (Dmp1 protein, mouse)
RN  - 0 (Extracellular Matrix Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Sost protein, mouse)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 104982-03-8 (Osteocalcin)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Apoptosis/physiology
MH  - Biomarkers
MH  - Biomechanical Phenomena
MH  - Calcification, Physiologic/*physiology
MH  - Caspase 3/genetics/metabolism
MH  - Extracellular Matrix Proteins/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation/physiology
MH  - Glycoproteins/genetics/metabolism
MH  - Homocysteine/administration & dosage/blood/*toxicity
MH  - Hyperhomocysteinemia/*metabolism
MH  - Intercellular Signaling Peptides and Proteins
MH  - Mice
MH  - Osteocalcin/genetics/metabolism
MH  - Osteocytes/*physiology
MH  - RNA, Messenger/genetics/metabolism
OTO - NOTNLM
OT  - Dmp1
OT  - E11
OT  - Sost
OT  - caspase 3
OT  - homocysteine
OT  - lacunae
OT  - osteocyte
EDAT- 2017/05/17 06:00
MHDA- 2017/09/12 06:00
CRDT- 2017/05/17 06:00
PHST- 2017/02/22 00:00 [received]
PHST- 2017/02/23 00:00 [accepted]
PHST- 2017/05/17 06:00 [entrez]
PHST- 2017/05/17 06:00 [pubmed]
PHST- 2017/09/12 06:00 [medline]
AID - 233/3/243 [pii]
AID - 10.1530/JOE-16-0562 [doi]
PST - ppublish
SO  - J Endocrinol. 2017 Jun;233(3):243-255. doi: 10.1530/JOE-16-0562.