A Novel H2S-releasing Amino-Bisphosphonate which combines bone anti-catabolic and anabolic functions.

Simona Rapposelli, Laura Gambari, Maria Digiacomo, Valentina Citi, Gina Lisignoli, Cristina Manferdini, Vincenzo Calderone, Francesco Grassi

Research output: Contribution to journalArticle

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Abstract

Bisphosphonates (BPs) are the first-line treatment of bone loss resulting from various pathological conditions. Due to their high affinity to bone they have been used to develop conjugates with pro-anabolic or anti-catabolic drugs. We recently demontrated that hydrogen sulfide (H2S), promotes osteogenesis and inhibits osteoclast differentiation. Here we developed an innovative molecule, named DM-22, obtained from the combination of alendronate (AL) and the H2S-releasing moiety aryl-isothiocyanate. DM-22 and AL were assayed in vitro in the concentration range 1-33 μM for effects on viability and function of human osteoclasts (h-OCs) and mesenchymal stromal cells (h-MSCs) undergoing osteogenic differentiation. Amperometric measures revealed that DM-22 releases H2S at a slow rate with a thiol-dependent mechanism. DM-22 significantly inhibited h-OCs differentiation and function, maintaining a residual h-OCs viability even at the high dose of 33 μM. Contrary to AL, in h-MSCs DM-22 did not induce cytotoxicity as revealed by LDH assay, significantly stimulated mineralization as measured by Alizarin Red staining and increased mRNA expression of Collagen I as compared to control cultures. In conclusion, DM-22 is a new BP which inhibits h-OCs function and stimulate osteogenic differentiation of h-MSCs, without cytotoxicity. DM-22 is an ideal candidate for a novel family of osteoanabolic drugs.
Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Sep 20 2017

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Diphosphonates
Osteoclasts
Alendronate
Bone and Bones
Mesenchymal Stromal Cells
Hydrogen Sulfide
Sulfhydryl Compounds
Osteogenesis
Pharmaceutical Preparations
Collagen
Staining and Labeling
Messenger RNA

Cite this

A Novel H2S-releasing Amino-Bisphosphonate which combines bone anti-catabolic and anabolic functions. / Rapposelli, Simona; Gambari, Laura; Digiacomo, Maria; Citi, Valentina; Lisignoli, Gina; Manferdini, Cristina; Calderone, Vincenzo; Grassi, Francesco.

In: Scientific Reports, Vol. 7, No. 1, 20.09.2017, p. 1-12.

Research output: Contribution to journalArticle

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