TY - JOUR
T1 - Enteroendocrine K Cells Exert Complementary Effects to Control Bone Quality and Mass in Mice
AU - Gobron, Benoit
AU - Bouvard, Beatrice
AU - Vyavahare, Sagar
AU - Blom, Liv V. V.
AU - Pedersen, Kristian K.
AU - Windelov, Johanne A.
AU - Boer, Geke A.
AU - Harada, Norio
AU - Zhang, Sheng
AU - Shimazu-Kuwahara, Satoko
AU - Wice, Burton
AU - Inagaki, Nobuya
AU - Legrand, Erick
AU - Flatt, Peter R.
AU - Chappard, Daniel
AU - Hartmann, Bolette
AU - Holst, Jens J.
AU - Rosenkilde, Mette M.
AU - Irwin, Nigel
AU - Mabilleau, Guillaume
PY - 2020
Y1 - 2020
N2 - The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. (c) 2020 American Society for Bone and Mineral Research.
AB - The involvement of a gut-bone axis in controlling bone physiology has been long suspected, although the exact mechanisms are unclear. We explored whether glucose-dependent insulinotropic polypeptide (GIP)-producing enteroendocrine K cells were involved in this process. The bone phenotype of transgenic mouse models lacking GIP secretion (GIP-GFP-KI) or enteroendocrine K cells (GIP-DT) was investigated. Mice deficient in GIP secretion exhibited lower bone strength, trabecular bone mass, trabecular number, and cortical thickness, notably due to higher bone resorption. Alterations of microstructure, modifications of bone compositional parameters, represented by lower collagen cross-linking, were also apparent. None of these alterations were observed in GIP-DT mice lacking enteroendocrine K cells, suggesting that another K-cell secretory product acts to counteract GIP action. To assess this, stable analogues of the known K-cell peptide hormones, xenin and GIP, were administered to mature NIH Swiss male mice. Both were capable of modulating bone strength mostly by altering bone microstructure, bone gene expression, and bone compositional parameters. However, the two molecules exhibited opposite actions on bone physiology, with evidence that xenin effects are mediated indirectly, possibly via neural networks. Our data highlight a previously unknown interaction between GIP and xenin, which both moderate gut-bone connectivity. (c) 2020 American Society for Bone and Mineral Research.
KW - BONE REMODELING
KW - ENTEROENDOCRINE SYSTEM
KW - GIP
KW - XENIN
KW - GASTRIC-INHIBITORY POLYPEPTIDE
KW - GLUCAGON-LIKE PEPTIDE-1
KW - NEUROTENSIN RECEPTOR
KW - INSULIN-RESISTANCE
KW - ACETYLCHOLINE
KW - EXPRESSION
KW - OSTEOBLAST
KW - SECRETION
KW - REDUCTION
U2 - 10.1002/jbmr.4004
DO - 10.1002/jbmr.4004
M3 - Journal article
C2 - 32155286
VL - 35
SP - 1363
EP - 1374
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
SN - 0884-0431
IS - 7
ER -