Neurotransmitter action in osteoblasts: expression of a functional system for serotonin receptor activation and reuptake

Bliziotes, Michael; Eshleman, Amy J.; Zhang, X.-W.; Wiren, Kristine M.

doi:10.1016/s8756-3282(01)00593-2

Cited by 201 publications

(170 citation statements)

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“…They also demonstrated that occupancy of the 5-HT 2B receptor stimulates proliferation of periosteal fibroblasts, and activation of 5-HT 2 receptors decreases nitric oxide synthesis in mechanically stimulated osteoblasts. We confirmed expression of 5-HT 2A and 5-HT 2B receptor proteins, and demonstrated that the 5-HT 1A and 5-HT 1D receptors and the 5-HTT are expressed in osteoblastic cells [23]. 5-HT receptors are expressed in both cultured osteoblastic cell lines and normal differentiating rat osteoblasts, and the 5-HTT is expressed in all osteoblastic cell lines examined.…”

Section: Introductionsupporting

confidence: 64%

“…We chose to evaluate expression of the 5-HT 1A and 5-HT 2A receptors because we previously demonstrated their expression in primary osteoblast cultures and osteoblastic cell lines [23]. 5-HTT expression was evaluated with a polyclonal antibody raised against a peptide mapping at the carboxy-terminus of the human serotonin transporter ( Figure 1A).…”

Section: Resultsmentioning

confidence: 99%

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Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells

Bliziotes

Eshleman

Burt‐Pichat

et al. 2006

Bone

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113

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Section: Introductionsupporting

confidence: 64%

Section: Resultsmentioning

confidence: 99%

Serotonin transporter and receptor expression in osteocytic MLO-Y4 cells

Bliziotes

Eshleman

Burt‐Pichat

et al. 2006

Bone

Self Cite

113

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“…(73) Dopamine transporter (Dat)-deficient mice manifest a low-bone-mass phenotype. (74) We therefore believe that this tantalizing finding should be explored further, whether or not there is a dopaminergic-related connection between the diseases. To further understand signaling cascades engaged by the most significant gene networks, we overlaid the canonical pathway genes with the gene network generated from our data set.…”

Section: Discussionmentioning

confidence: 92%

Identification of homogeneous genetic architecture of multiple genetically correlated traits by block clustering of genome-wide associations

Gupta

Cheung

Hsu

et al. 2011

Journal of Bone and Mineral Research

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Genome-wide association studies (GWAS) using high-density genotyping platforms offer an unbiased strategy to identify new candidate genes for osteoporosis. It is imperative to be able to clearly distinguish signal from noise by focusing on the best phenotype in a genetic study. We performed GWAS of multiple phenotypes associated with fractures [bone mineral density (BMD), bone quantitative ultrasound (QUS), bone geometry, and muscle mass] with approximately 433,000 single-nucleotide polymorphisms (SNPs) and created a database of resulting associations. We performed analysis of GWAS data from 23 phenotypes by a novel modification of a block clustering algorithm followed by gene-set enrichment analysis. A data matrix of standardized regression coefficients was partitioned along both axes-SNPs and phenotypes. Each partition represents a distinct cluster of SNPs that have similar effects over a particular set of phenotypes. Application of this method to our data shows several SNP-phenotype connections. We found a strong cluster of association coefficients of high magnitude for 10 traits (BMD at several skeletal sites, ultrasound measures, cross-sectional bone area, and section modulus of femoral neck and shaft). These clustered traits were highly genetically correlated. Gene-set enrichment analyses indicated the augmentation of genes that cluster with the 10 osteoporosis-related traits in pathways such as aldosterone signaling in epithelial cells, role of osteoblasts, osteoclasts, and chondrocytes in rheumatoid arthritis, and Parkinson signaling. In addition to several known candidate genes, we also identified PRKCH and SCNN1B as potential candidate genes for multiple bone traits. In conclusion, our mining of GWAS results revealed the similarity of association results between bone strength phenotypes that may be attributed to pleiotropic effects of genes. This knowledge may prove helpful in identifying novel genes and pathways that underlie several correlated phenotypes, as well as in deciphering genetic and phenotypic modularity underlying osteoporosis risk. ß

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“…Corticosteroids, cytokines, and serotonin have been postulated to play a role in both depression [3][4][5][6] and bone homeostasis. [7][8][9][10][11] Alternatively, the link could be caused by factors associated with depression that affect bone health such as inactivity, nutrition, weight, calcium intake, or smoking. Antidepressants may also have a direct effect on bone through serotonin pathways 12,13 or have a complex relationship through falls or depressive symptomatology and severity.…”

Section: Introductionmentioning

confidence: 99%