期刊
JOURNAL OF CELLULAR PHYSIOLOGY
卷 236, 期 6, 页码 4614-4624出版社
WILEY
DOI: 10.1002/jcp.30194
关键词
bone‐ fat interactions; genetic animal models; matrix mineralization; non‐ collagenous proteins; osteoblasts
资金
- British Heart Foundation [PG/15/13/31296]
- Tenovus Scotland [E17/03]
- Biotechnology and Biological Sciences Research Council [BB/J004316/1, BBS/E/D/20221657, BB/P02503X/1]
Female mice lacking osteoblast NPP1 expression showed increased bone volume and reduced trabecular spacing, while male mice were unaffected. Osteoblast NPP1 plays a crucial role in skeletal development and has a secondary metabolic impact that predominantly maintains insulin sensitivity.
Supraphysiological levels of the osteoblast-enriched mineralization regulator ectonucleotide pyrophosphatase or phosphodiesterase-1 (NPP1) is associated with type 2 diabetes mellitus. We determined the impact of osteoblast-specific Enpp1 ablation on skeletal structure and metabolic phenotype in mice. Female, but not male, 6-week-old mice lacking osteoblast NPP1 expression (osteoblast-specific knockout [KO]) exhibited increased femoral bone volume or total volume (17.50% vs. 11.67%; p < .01), and reduced trabecular spacing (0.187 vs. 0.157 mm; p < .01) compared with floxed (control) mice. Furthermore, an enhanced ability of isolated osteoblasts from the osteoblast-specific KO to calcify their matrix in vitro compared to fl/fl osteoblasts was observed (p < .05). Male osteoblast-specific KO and fl/fl mice showed comparable glucose and insulin tolerance despite increased levels of insulin-sensitizing under-carboxylated osteocalcin (195% increase; p < .05). However, following high-fat-diet challenge, osteoblast-specific KO mice showed impaired glucose and insulin tolerance compared with fl/fl mice. These data highlight a crucial local role for osteoblast NPP1 in skeletal development and a secondary metabolic impact that predominantly maintains insulin sensitivity.
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