Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032, USA.
Calcif Tissue Int. 2010 May;86(5):382-8. doi: 10.1007/s00223-010-9350-7. Epub 2010 Mar 24.
The low-density lipoprotein receptor-related protein (Lrp)-5 regulates osteoblast proliferation and bone formation through its expression in duodenum by modifying the gut serotonin-bone endocrine axis. However, its direct role, if any, in osteoblast progenitor cells has not been studied thus far. Here, we show that mice with a Dermo1-Cre-mediated disruption of Lrp5 in osteoblast progenitor cells have normal embryonic skeletogenesis and normal skeletal growth and development postnatally. Histomorphometric analysis of 3-month-old adult mice revealed normal osteoblast numbers, bone formation rate, and bone mass in Lrp5(Dermo)(-/-) mice. In addition, analysis of two osteoporosis pseudoglioma (OPPG) patients revealed a three- to fivefold increase in their serum serotonin levels compared to age-matched controls. These results rule out a direct function of Lrp5 in osteoblast progenitor cells and add further support to the notion that dysregulation of serotonin synthesis is involved in bone mass abnormalities observed in OPPG patients.
低密度脂蛋白受体相关蛋白 (Lrp)-5 通过在十二指肠中表达来调节骨细胞增殖和骨形成，通过调节肠道 5-羟色胺-骨骼内分泌轴。然而，迄今为止，其在成骨细胞祖细胞中的直接作用尚不清楚。在这里，我们表明，在成骨细胞祖细胞中通过 Dermo1-Cre 介导的 Lrp5 缺失的小鼠具有正常的胚胎骨骼发生和出生后正常的骨骼生长和发育。对 3 个月大的成年小鼠进行组织形态计量学分析表明，Lrp5(Dermo)(-/-) 小鼠的成骨细胞数量、骨形成率和骨量正常。此外，对两名骨质疏松性假瘤 (OPPG) 患者的分析表明，与年龄匹配的对照组相比，他们的血清 5-羟色胺水平增加了三到五倍。这些结果排除了 Lrp5 在成骨细胞祖细胞中的直接作用，并进一步支持这样一种观点，即 5-羟色胺合成的失调参与了 OPPG 患者中观察到的骨量异常。
