Cell adhesion molecule 1 is a new osteoblastic cell adhesion molecule and a diagnostic marker for osteosarcoma

Inoué, Takao; Hagiyama, Man; Enoki, Eisuke; Sakurai, Minami A.; Tan, Akihiro; Wakayama, Tomohiko; Iseki, Shoichi; Murakami, Yoshinori; Fukuda, Kanji; Hamanishi, Chiaki; Ito, Akihiko

doi:10.1016/j.lfs.2012.10.021

Cited by 37 publications

(35 citation statements)

References 39 publications

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“…Cadm1 in human overlaps an association for estimated BMD. In the context of osteosarcoma, Cadm1 is expressed on the osteoblast cell surface and is used as a marker of differentiation . Additionally, Cadm1 plays a role in NFATc1 modulation of osteoclast activity …”

Section: Resultsmentioning

confidence: 99%

Genetic Dissection of Femoral and Tibial Microarchitecture

Huang

et al. 2019

JBMR Plus

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Our understanding of the genetic control of bone strength has relied mainly on estimates of bone mineral density. Here we have mapped genetic factors that influence femoral and tibial microarchitecture using high‐resolution x‐ray computed tomography (8‐μm isotropic voxels) across a family of 61 BXD strains of mice, roughly 10 isogenic cases per strain and balanced by sex. We computed heritabilities for 25 cortical and trabecular traits. Males and females have well‐matched heritabilities, ranging from 0.25 to 0.75. We mapped 16 genetic loci most of which were detected only in females. There is also a bias in favor of loci that control cortical rather than trabecular bone. To evaluate candidate genes, we combined well‐established gene ontologies with bone transcriptome data to compute bone‐enrichment scores for all protein‐coding genes. We aligned candidates with those of human genome‐wide association studies. A subset of 50 strong candidates fell into three categories: (1) experimentally validated genes already known to modulate bone function (Adamts4, Ddr2, Darc, Adam12, Fkbp10, E2f6, Adam17, Grem2, Ifi204); (2) candidates without any experimentally validated function in bone (eg, Greb1, Ifi202b), but linked to skeletal phenotypes in human cohorts; and (3) candidates that have high bone‐enrichment scores, but for which there is not yet any functional link to bone biology or skeletal system disease (including Ifi202b, Ly9, Ifi205, Mgmt, F2rl1, Iqgap2). Our results highlight contrasting genetic architecture between sexes and among major bone compartments. The alignment of murine and human data facilitates function analysis and should prove of value for preclinical testing of molecular control of bone structure. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

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Section: Resultsmentioning

confidence: 99%

Genetic Dissection of Femoral and Tibial Microarchitecture

Huang

et al. 2019

JBMR Plus

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“…Cadm1 is located on chromosome 9 in mouse, on chromosome 11 in human, and overlaps an association for estimated BMD on chromosome 11 spanning from 115-115.2 Mbp and is just upstream of an association spanning from 115.4-115.6 Mbp. In the context of osteosarcoma, Cadm1 has been observed on the osteoblast cell surface and has been used as a marker of differentiation in osteoblasts (81) . Additionally, Cadm1 has been demonstrated to play a role in NFATc1 regulation of osteoclast activity (82) .…”

Section: Combined Analysis Of Mouse Candidate Genes With Qtls and Gwamentioning

confidence: 99%

Genetic dissection of femoral and tibial microarchitecture

Huang

et al. 2019

Preprint

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Our understanding of the genetic control of bone has relied almost exclusively on estimates of bone mineral density. In contrast, here we have used high-resolution x-ray tomography (8 µm isotropic voxels) to measure femoral and tibial components across a set of ~600 mice belonging to 60 diverse BXD strains of mice. We computed heritabilities of 25 cortical and trabecular compartments. Males and females have well matched trait heritabilities, ranging from 0.25 to 0.75. We mapped 16 QTLs that collectively cover ~8% of all protein-coding genes in mouse. A majority of loci are detected only in females, and there is also a bias in favor of QTLs for cortical traits. To efficiently evaluate candidate genes we developed a method that couples gene ontologies with expression data to compute boneenrichment scores for almost all protein-coding genes. We carefully collated and aligned murine candidates with recent human BMD genome-wide association results. We highlight a subset of 50 strong candidates that fall into three categories: 1. those linked to bone function that have already been experimentally validated (Adamts4, Ddr2, Darc, Adam12, Fkbp10, E2f6, Adam17, Grem2, Ifi204); 2. candidates with putative bone function but not yet tested (e.g., Greb1, Ifi202b) but several of which have been linked to phenotypes in humans; and 3. candidates that have high bone-enrichment scores but for which there is not yet any specific link to bone biology or skeletal disease, including Ifi202b, Ly9, Ifi205, Mgmt, F2rl1, Iqgap2. Our results highlight contrasting genetic architecture between the sexes and among major bone compartments. The joint use and alignment of murine and human data should greatly facilitate function analysis and preclinical testing.

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“…Almost all OS patients may develop micrometastasis at initial diagnosis, and the early detection of micrometastasis may allow the prognosis and early treatment to prevent local relapse and metastasis. In this regard, the use of biological marker may identify the disease at an earlier stage and may develop effective treatments for the patients with OS [40]. OPN can serve as a promising molecular marker for the diagnosis of OS which is down-regulated during osteoblastic maturation [19,20] and up-regulated during metastatic OS [21,22].…”

Section: Osteopontin As a Target In Osteosarcoma Therapeuticsmentioning

confidence: 99%

Role of osteopontin in osteosarcoma

Deng

Zeng

et al. 2014

Med Oncol

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The primary bone malignancy osteosarcoma (OS) is a painful health burden, of which treatment remains a challenging problem. Identification of specific tumor biomarkers may help to investigate and develop the novel effective therapeutic approaches that have specific molecular target for the treatment of patients with OS. Osteopontin (OPN), a phosphorylated glycoprotein, is involved in many biological processes, such as biomineralization, bone remodeling and immune responses and has recently been reported to be associated with OS pathogenesis. Interestingly, both of the up- and down-regulation of OPN are involved in OS. During OS development, genetic or epigenetic disruption causes reduced expression of RUNX2 and OPN through the up-regulation of notch signaling pathway, leading to the development of OS. On the other hand, during hypoxic condition, upregulation of OPN induces the glucose uptake into hypoxic OS cells which is responsible for the OS cell proliferation and drug resistance. Recent evidences show that targeting OPN might be an important tool in OS therapeutics. This review has focused on the association of abnormal OPN expression with the pathogenesis of OS, the efficiency of OPN as a diagnostic tool for OS and the therapeutic aspects of OS by targeting OPN.

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Cell adhesion molecule 1 is a new osteoblastic cell adhesion molecule and a diagnostic marker for osteosarcoma

Cited by 37 publications

References 39 publications

Genetic Dissection of Femoral and Tibial Microarchitecture

Genetic Dissection of Femoral and Tibial Microarchitecture

Genetic dissection of femoral and tibial microarchitecture

Role of osteopontin in osteosarcoma

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