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October 30, 2024
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Osteostatin Inhibits M-CSF plus RANKL-Induced Human Osteoclast Differentiation by Modulating NFATc1

Publicated to: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. 23 (15): 8551- - 2022-08-01 23(15), DOI: 10.3390/ijms23158551

Authors:

Ibáñez, L; Nácher-Juan, J; Terencio, MC; Ferrándiz, ML; Alcaraz, MJ
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Affiliations

Cardenal Herrera CEU Univ, Dept Pharm - Author
Univ Valencia, Polytech Univ Valencia, Interuniv Res Inst Mol Recognit & Technol Dev IDM - Author

Abstract

Parathyroid hormone-related protein (PTHrP) C-terminal peptides regulate the metabolism of bone cells. PHTrP [107-111] (osteostatin) promotes bone repair in animal models of bone defects and prevents bone erosion in inflammatory arthritis. In addition to its positive effects on osteoblasts, osteostatin may inhibit bone resorption. The aim of this study was to determine the effects of osteostatin on human osteoclast differentiation and function. We used macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL) to induce the osteoclast differentiation of adherent human peripheral blood mononuclear cells. Tartrate-resistant acid phosphatase (TRAP) staining was performed for the detection of the osteoclasts. The function of mature osteoclasts was assessed with a pit resorption assay. Gene expression was evaluated with qRT-PCR, and nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) nuclear translocation was studied by immunofluorescence. We observed that osteostatin (100, 250 and 500 nM) decreased the differentiation of osteoclasts in a concentration-dependent manner, but it did not modify the resorptive ability of mature osteoclasts. In addition, osteostatin decreased the mRNA levels of cathepsin K, osteoclast associated Ig-like receptor (OSCAR) and NFATc1. The nuclear translocation of the master transcription factor in osteoclast differentiation NFATc1 was reduced by osteostatin. Our results suggest that the anti-resorptive effects of osteostatin may be dependent on the inhibition of osteoclastogenesis. This study has shown that osteostatin controls human osteoclast differentiation in vitro through the downregulation of NFATc1.
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Keywords

Acid phosphatase tartrate resistant isoenzymeAnimalAnimalsArticleBoneBone resorptionBone-resorptionCarboxyl-terminal peptideCathepsin kCell differentiationCell functionCellsColony stimulating factor 1Controlled studyDown regulationFragmentsGene expressionGlyceraldehyde 3 phosphate dehydrogenaseHormone-related proteinHumanHuman cellHumansImmunofluorescenceImprovesIn vitro studyLeukocytes, mononuclearMacrophage colony-stimulating factorMessenger rnaMetabolismMononuclear cellNfatc transcription factorsNfatc1Nfatc1 protein, humanNuclear factor of activated t cells cytoplasmic 1Optical densityOsteoclastOsteoclast associated ig like receptorOsteoclast differentiation factorOsteoclastogenesisOsteoclastsOsteolysisOsteostatinParathyroid hormone related proteinParathyroid hormone-related proteinParathyroid hormone-related protein (107-111)Peptide fragmentPeptide fragmentsPeripheral blood mononuclear cellPthrp 107-139Pthrp c-terminal peptidesRank ligandRatReal time polymerase chain reactionReceptorsRegenerationTranscription factorTranscription factor nfatUnclassified drug

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2022, it was in position 66/285, thus managing to position itself as a Q1 (Primer Cuartil), in the category Biochemistry & Molecular Biology.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.27. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.52 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-04-02, the following number of citations:

  • WoS: 15
  • Scopus: 19
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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-02:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 11 (PlumX).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: Last Author (Alcaraz, MJ).

the authors responsible for correspondence tasks have been Ferrándiz, ML and Alcaraz, MJ.

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