PMID- 34388585
OWN - NLM
STAT- MEDLINE
DCOM- 20211209
LR  - 20220531
IS  - 1873-1244 (Electronic)
IS  - 0899-9007 (Linking)
VI  - 91-92
DP  - 2021 Nov-Dec
TI  - Bone mass protective potential mediated by bovine milk basic protein requires 
      normal calcium homeostasis in mice.
PG  - 111409
LID - S0899-9007(21)00271-9 [pii]
LID - 10.1016/j.nut.2021.111409 [doi]
AB  - OBJECTIVES: Milk provide protective effects against bone loss caused by an 
      impaired calcium balance. Although the effects of some elements have previously 
      been confirmed, the involvement of milk basic protein (MBP) in bone mineral 
      metabolism remains poorly characterized. Moreover, the importance of mineral 
      nutrition sufficiency to establish the effect of MBP must be evaluated. METHODS: 
      First, to evaluate the physiological conditions required for MBP activity, we 
      examined the bone and mineral phenotypes of mice that suffer from insufficient 
      calcium absorption due to a lack of intestinal vitamin D signaling. Second, to 
      determine whether vitamin D signaling affects the effect of MBP on bone 
      resorption, in vitro osteoclastogenesis were assessed using bone marrow cells. 
      RESULTS: In mice with systemic vitamin D receptor (Vdr) inactivation, dietary MBP 
      supplementation was unable to normalize hypercalcemia and hyperparathyroidism and 
      failed to rescue bone mineralization impairments. In contrast, calcium and bone 
      homeostasis responded to MBP supplementation when Vdr inactivation was restricted 
      to the intestines. Hyperparathyroidism in intestine-specific Vdr knockout mice 
      was also improved by MBP supplementation, along with a decrease in bone 
      resorption in response to the level of serum tartrate-resistant acid phosphatase 
      5b. These results corresponded with a reduction in tartrate-resistant acid 
      phosphatase-stained osteoclast numbers and the eroded surface on the tibia. MBP 
      treatment dose-dependently suppressed osteoclastogenesis in cultured bone marrow 
      macrophages regardless of vitamin D activity. These effects of MBP were blunted 
      when parathyroid hormone was added to the culture medium, which is in line with 
      the in vivo phenotype observed with systemic Vdr inactivation and suggests that 
      severe hyperparathyroidism limits MBP activity in the bone. CONCLUSIONS: 
      Therefore, adaptive calcium homeostasis is an essential requirement when MBP 
      exerts protective effects through the inhibition of bone resorption.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Ono-Ohmachi, Aiko
AU  - Ono-Ohmachi A
AD  - Milk Science Research Institute, Megmilk Snow Brand Co., Ltd., Saitama, Japan; 
      Department of Quality Assurance, Bean Stalk Snow Co., Ltd., Tokyo, Japan.
FAU - Ishida, Yuko
AU  - Ishida Y
AD  - Milk Science Research Institute, Megmilk Snow Brand Co., Ltd., Saitama, Japan.
FAU - Morita, Yoshikazu
AU  - Morita Y
AD  - Milk Science Research Institute, Megmilk Snow Brand Co., Ltd., Saitama, Japan.
FAU - Kato, Ken
AU  - Kato K
AD  - Milk Science Research Institute, Megmilk Snow Brand Co., Ltd., Saitama, Japan.
FAU - Yamanaka, Hitoki
AU  - Yamanaka H
AD  - Research Center for Support to Advanced Science, Shinshu University, Nagano, 
      Japan.
FAU - Masuyama, Ritsuko
AU  - Masuyama R
AD  - Department of Molecular Bone Biology, Nagasaki University Graduate School of 
      Biomedical Sciences, Nagasaki, Japan; Ritsumeikan University, Graduate school of 
      Gastronomy Management, Shiga, Japan.
LA  - eng
PT  - Journal Article
DEP - 20210702
PL  - United States
TA  - Nutrition
JT  - Nutrition (Burbank, Los Angeles County, Calif.)
JID - 8802712
RN  - 0 (Milk Proteins)
RN  - 0 (Receptors, Calcitriol)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Animals
MH  - *Bone Density
MH  - *Calcium
MH  - Homeostasis
MH  - Mice
MH  - Mice, Knockout
MH  - Milk
MH  - *Milk Proteins
MH  - Receptors, Calcitriol
OTO - NOTNLM
OT  - VDR knockout mice
OT  - Whey protein
OT  - bone mineral metabolism
OT  - calcium status
OT  - parathyroid hormone
OT  - vitamin D receptor
COIS- Declaration of interests The authors declare that they have no known competing 
      financial interests or personal relationships that could have appeared to 
      influence the work reported in this paper.
EDAT- 2021/08/14 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/08/13 20:17
PHST- 2020/11/02 00:00 [received]
PHST- 2021/06/21 00:00 [revised]
PHST- 2021/06/25 00:00 [accepted]
PHST- 2021/08/14 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/08/13 20:17 [entrez]
AID - S0899-9007(21)00271-9 [pii]
AID - 10.1016/j.nut.2021.111409 [doi]
PST - ppublish
SO  - Nutrition. 2021 Nov-Dec;91-92:111409. doi: 10.1016/j.nut.2021.111409. Epub 2021 
      Jul 2.