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Osteoclast Determinants and Implications for Therapy

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Osteoimmunology

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Abstract

Osteoclasts are multinucleated cells which contribute to bone remodeling by the erosion of the mineralized matrix. They belong to the hematopoietic cell lineage, arising from the monocyte/macrophage precursor family. Polarization and adhesion to substrate are mandatory events for bone resorption, which occurs extracellularly in an area underneath the cell, denominated resorbing lacuna. This is an acidic microenvironment in which low pH allows at the same time the dissolution of the inorganic hydroxyapatite matrix and the activity of enzymes that degrade the organic components, especially collagen. Osteoclastogenesis is subjected to regulation by the RANKL/RANK axis, which links osteoclasts to the immune system. Both exacerbated and impaired osteoclast activity are deleterious for the skeleton, with consequent perturbations of bone remodeling. In both cases, therapy is not yet satisfactory and it is urgent to identify new and specific determinants that may contribute to understand the etiology of osteoclast disorders, and that could be targeted for therapy. Specificity of treatments is an issue because many cells share common determinants that are likely to cause adverse effects when disturbed. Intense osteoclast research is in progress and is expected to led shortly to new knowledge with high translational impact.

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Abbreviations

CAII:

Carbonic anhydrase II

CLC7:

Chloride channel type 7

CtpK:

Cathepsin K gene

DC-STAMP:

Dendritic cell-specific transmembrane protein

ERK:

Extracellular signal-regulated kinase

JNK:

c-Jun N-terminal kinase

MAPK:

Mitogen-activated protein kinase

M-CSF:

Macrophage colony-stimulating factor

MFR:

Macrophage fusion receptor

MITF:

Microphthalmia-associated transcription factor

MMPs:

Metalloproteinases

NEMO:

NF-κβ essential modulator

NF-kB:

Nuclear factor-kB

OSTM1:

Osteopetrosis associated transmembrane protein 1

PLEKHM1:

Pleckstrin homology domain containing, family M (with RUN domain) member 1

PRELP:

Proline/arginine-rich end leucine-rich repeat protein

RANK:

Receptor activator of NF-kappaB

RANKL:

Receptor activator of NF-kappaB ligand

RGD:

Amino acid sequence Arg-Gly-Asp

S1P:

Sphingosine-1-phosphate

SERM:

Selective estrogen receptor modulator

SIRP:

Signal-regulatory-protein

TCIRG1:

T-cell immune regulator 1

TFGβ:

Transforming growth factor β

TNFSF11:

Tumor necrosis factor ligand superfamily, member 11

TNFRSF11A:

Tumor necrosis factor receptor superfamily, member 11A

TRAcP:

Tartrate-resistant acid phosphatase

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Acknowledgments

The original work was supported by grants from the EC (OSTEOGENE, contract No. LSHM-CT-2003-502941), the Italian Association for Cancer Research and the Swiss Bridge Foundation.

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Authors and Affiliations

  1. Department of Biotechnological and Applied Clinical Sciences, University of L’Aquila, Via Vetoio – Coppio 2, 67100, L’Aquila, Italy

    Anna Teti

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  1. Anna Teti
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Correspondence to Anna Teti .

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Editors and Affiliations

  1. School of Medicine, Dept. Pathology & Lab. Medicine, University of Pennsylvania, Curie Blvd., Philadelphia, 19104, Pennsylvania, USA

    Yongwon Choi

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Teti, A. (2013). Osteoclast Determinants and Implications for Therapy. In: Choi, Y. (eds) Osteoimmunology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5366-6_14

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