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LRP5 Controls Bone Formation By Inhibiting Serotonin Synthesis In The Duodenum

Discussion in 'Articles & Scientific Studies' started by paymanz, Apr 19, 2016.

  1. paymanz

    paymanz Member

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    LRP5 - Wikipedia

    im so interest to find any info on how increase Lrp5(it strongly inhibit gut serotonin release) , only thing i found that upregulates the synthesis of it is vitamin D, and also Cholesterol.
    but who knows, maybe serotonin lowering effect of salt works through this pathway.

    Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. - PubMed - NCBI

    Abstract
    Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation, causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor, osteoblast-specific disruption of beta-Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice, and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a beta-Catenin-independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner, this study broadens our understanding of bone remodeling and suggests potential therapies to increase bone mass.


    1,25-Dihydroxyvitamin D3 regulates the expression of low-density lipoprotein receptor-related protein 5 via deoxyribonucleic acid sequence elements... - PubMed - NCBI

    Low-density lipoprotein receptor-related protein 5 (LRP5) expression in human osteoarthritic chondrocytes. - PubMed - NCBI

    another interesting thing i found is that in some of articles they claim brain serotonin actually has positive effect on bone unlike gut serotonin.
    im not sure what is ray's stand for brain serotonin?

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    Vitamin D Lowers Gut Serotonin But Increases Brain Serotonin


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    Doxycycline induces bone repair and changes in Wnt signalling
     
  2. julio

    julio New Member

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    Has somebody tried this? I have osteoarthritis. Thanks
     
  3. OP
    paymanz

    paymanz Member

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    Curcumin increases LRP5

    Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling. - PubMed - NCBI


    Abstract

    Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.
     
  4. REOSIRENS

    REOSIRENS Member

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    Curcumin is a 5ar inhibitor... Everytime I drink tea with this substance it greatly helps fighting hair loss but causes massive depression
     
  5. OP
    paymanz

    paymanz Member

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    Mmm bad, none of these herbs and spices are without a downside!
     
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