PMID- 28931828
OWN - NLM
STAT- MEDLINE
DCOM- 20190627
LR  - 20190627
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Sep 20
TI  - A Novel H2S-releasing Amino-Bisphosphonate which combines bone anti-catabolic and 
      anabolic functions.
PG  - 11940
LID - 10.1038/s41598-017-11608-z [doi]
LID - 11940
AB  - 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 (H(2)S), promotes osteogenesis and 
      inhibits osteoclast differentiation. Here we developed an innovative molecule, 
      named DM-22, obtained from the combination of alendronate (AL) and the 
      H(2)S-releasing moiety aryl-isothiocyanate. DM-22 and AL were assayed in vitro in 
      the concentration range 1-33 muM 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 H(2)S 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 muM. 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.
FAU - Rapposelli, Simona
AU  - Rapposelli S
AUID- ORCID: 0000-0003-0146-6358
AD  - Dipartimento di Farmacia, Universita di Pisa, Via Bonanno 6, I-56126, Pisa, 
      Italy.
FAU - Gambari, Laura
AU  - Gambari L
AD  - Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136, 
      Bologna, Italy.
FAU - Digiacomo, Maria
AU  - Digiacomo M
AD  - Dipartimento di Farmacia, Universita di Pisa, Via Bonanno 6, I-56126, Pisa, 
      Italy.
FAU - Citi, Valentina
AU  - Citi V
AD  - Dipartimento di Farmacia, Universita di Pisa, Via Bonanno 6, I-56126, Pisa, 
      Italy.
FAU - Lisignoli, Gina
AU  - Lisignoli G
AD  - S.C. Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto 
      Ortopedico Rizzoli, Via di Barbiano 1/10, 40136, Bologna, Italy.
FAU - Manferdini, Cristina
AU  - Manferdini C
AD  - S.C. Laboratorio di Immunoreumatologia e Rigenerazione Tissutale, Istituto 
      Ortopedico Rizzoli, Via di Barbiano 1/10, 40136, Bologna, Italy.
FAU - Calderone, Vincenzo
AU  - Calderone V
AD  - Dipartimento di Farmacia, Universita di Pisa, Via Bonanno 6, I-56126, Pisa, 
      Italy.
FAU - Grassi, Francesco
AU  - Grassi F
AD  - Laboratorio RAMSES, Istituto Ortopedico Rizzoli, Via di Barbiano 1/10, 40136, 
      Bologna, Italy. francesco.grassi@ior.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170920
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - 0 (Isothiocyanates)
RN  - 3129-90-6 (isothiocyanic acid)
RN  - X1J18R4W8P (Alendronate)
RN  - YY9FVM7NSN (Hydrogen Sulfide)
SB  - IM
MH  - Alendronate/metabolism
MH  - Bone Density Conservation Agents/chemical synthesis/*metabolism
MH  - Cell Differentiation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Diphosphonates/chemical synthesis/*metabolism
MH  - Humans
MH  - Hydrogen Sulfide/*metabolism
MH  - Isothiocyanates/metabolism
MH  - Mesenchymal Stem Cells/drug effects
MH  - Osteoclasts/drug effects
MH  - Osteogenesis/*drug effects
PMC - PMC5607332
COIS- The authors declare that they have no competing interests.
EDAT- 2017/09/22 06:00
MHDA- 2019/06/30 06:00
PMCR- 2017/09/20
CRDT- 2017/09/22 06:00
PHST- 2017/05/30 00:00 [received]
PHST- 2017/08/25 00:00 [accepted]
PHST- 2017/09/22 06:00 [entrez]
PHST- 2017/09/22 06:00 [pubmed]
PHST- 2019/06/30 06:00 [medline]
PHST- 2017/09/20 00:00 [pmc-release]
AID - 10.1038/s41598-017-11608-z [pii]
AID - 11608 [pii]
AID - 10.1038/s41598-017-11608-z [doi]
PST - epublish
SO  - Sci Rep. 2017 Sep 20;7(1):11940. doi: 10.1038/s41598-017-11608-z.