Abstract
Recently, reports published in Nature Medicine and Cell have suggested the existence of a gut-bone axis based on studies of gene knockout mice. First, impaired gastric acid secretion was claimed to negatively affect calcium homeostasis and bone mass; which was based on the bone phenotype of cholecystokinin-B (or 2) receptor knockout mice. However, also histidine decarboxylase knockout mice suffered from impaired gastric acid secretion, while exhibiting a very different bone phenotype. This argues against the view that lack of gastric acid causes bone loss. Second, circulating serotonin was claimed to inhibit bone formation. This claim was based on the observation that mice deficient in low-density lipoprotein receptor-related protein 5 (Lrp5) exhibited bone loss coupled with accelerated serotonin synthesis. Lrp5 was claimed to control bone formation by a link involving duodenal serotonin synthesis. However, the accelerated serotonin synthesis in Lrp5 knockouts occurred after the onset of bone loss, a sequence of events that does not suggest a causal relationship between elevated serotonin in blood and bone loss. Moreover, pharmacological inhibition of serotonin synthesis prevented bone loss following ovariectomy in wild-type mice and rats, an observation that does not support the existence of Lrp5 pathway in the serotonin- bone axis.
Keywords: Bone, CCK2 receptor, histidine decarboxylase, gastric acid, Lrp5, serotonin, cholecystokinin-B, homeostasis, lipoprotein, Osteopetrosis, hypopituitarism, malnutrition, malabsorption, hypogonadism, weightlessness, phenotypes, osteosclerotic, tyrosine, homozygotes
Current Pharmaceutical Design
Title: The Possible Existence of a Gut-Bone Axis Suggested by Studies of Genetically Manipulated Mouse Models?
Volume: 17 Issue: 16
Author(s): Duan Chen and Chun-Mei Zhao
Affiliation:
Keywords: Bone, CCK2 receptor, histidine decarboxylase, gastric acid, Lrp5, serotonin, cholecystokinin-B, homeostasis, lipoprotein, Osteopetrosis, hypopituitarism, malnutrition, malabsorption, hypogonadism, weightlessness, phenotypes, osteosclerotic, tyrosine, homozygotes
Abstract: Recently, reports published in Nature Medicine and Cell have suggested the existence of a gut-bone axis based on studies of gene knockout mice. First, impaired gastric acid secretion was claimed to negatively affect calcium homeostasis and bone mass; which was based on the bone phenotype of cholecystokinin-B (or 2) receptor knockout mice. However, also histidine decarboxylase knockout mice suffered from impaired gastric acid secretion, while exhibiting a very different bone phenotype. This argues against the view that lack of gastric acid causes bone loss. Second, circulating serotonin was claimed to inhibit bone formation. This claim was based on the observation that mice deficient in low-density lipoprotein receptor-related protein 5 (Lrp5) exhibited bone loss coupled with accelerated serotonin synthesis. Lrp5 was claimed to control bone formation by a link involving duodenal serotonin synthesis. However, the accelerated serotonin synthesis in Lrp5 knockouts occurred after the onset of bone loss, a sequence of events that does not suggest a causal relationship between elevated serotonin in blood and bone loss. Moreover, pharmacological inhibition of serotonin synthesis prevented bone loss following ovariectomy in wild-type mice and rats, an observation that does not support the existence of Lrp5 pathway in the serotonin- bone axis.
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Cite this article as:
Chen Duan and Zhao Chun-Mei, The Possible Existence of a Gut-Bone Axis Suggested by Studies of Genetically Manipulated Mouse Models?, Current Pharmaceutical Design 2011; 17 (16) . https://dx.doi.org/10.2174/138161211796196972
DOI https://dx.doi.org/10.2174/138161211796196972 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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