Bone Biology Laboratory, Cátedra de Química Biológica, Facultad de Ciencias Médicas, School of Medicine, Rosario National University, Santa Fe 3100, 2000, Rosario, Argentina.
National Council of Scientific and Technical Research (CONICET), Rosario, Argentina.
J Bone Miner Metab. 2018 Nov;36(6):661-667. doi: 10.1007/s00774-017-0887-7. Epub 2017 Dec 12.
Previous studies have demonstrated a negative correlation between intestinal alkaline phosphatase (IAP) activity and calcium (Ca) absorption in the gut, as IAP acts as a protective mechanism inhibiting high Ca entry into enterocytes, preventing Ca overload. Here we evaluated Ca absorption and bone properties in knockout mice (KO) completely devoid of duodenal IAP (Akp3 mice). Female C57BL/6 control mice (WT, n = 7) and KO mice (n = 10) were used to determine Ca absorption in vivo and by in situ isolated duodenal loops followed by histomorphometric analysis of duodenal villi and crypts. Bone mineral density, morphometry, histomorphometry and trabecular connectivity and biomechanical properties were measured on bones. We observed mild atrophy of the villi with lower absorption surface and a significantly higher Ca uptake in KO mice. While no changes were seen in cortical bone, we found better trabecular connectivity and biomechanical properties in the femurs of KO mice compared to WT mice. Our data indicate that IAP KO mice display higher intestinal Ca uptake, which over time appears to correlate with a positive effect on the biomechanical properties of trabecular bone.
先前的研究表明，肠道碱性磷酸酶（IAP）活性与肠道钙（Ca）吸收呈负相关，因为 IAP 作为一种保护机制，抑制高钙进入肠细胞，防止钙过载。在这里，我们评估了缺乏十二指肠 IAP 的敲除小鼠（Akp3 小鼠）中的 Ca 吸收和骨骼特性。使用雌性 C57BL/6 对照小鼠（WT，n=7）和敲除小鼠（n=10）来确定体内和原位分离的十二指肠肠袢中的 Ca 吸收，随后对十二指肠绒毛和隐窝进行组织形态计量学分析。对骨骼进行骨密度、形态计量学、组织形态计量学和小梁连通性以及生物力学特性的测量。我们观察到 KO 小鼠的绒毛轻度萎缩，吸收表面积更低，但 Ca 摄取量明显更高。虽然皮质骨没有变化，但与 WT 小鼠相比，KO 小鼠的股骨具有更好的小梁连通性和生物力学特性。我们的数据表明，IAP 敲除小鼠表现出更高的肠道 Ca 摄取，随着时间的推移，这似乎与小梁骨的生物力学特性的积极影响相关。
