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Bone Abstracts (2016) 5 P416 | DOI: 10.1530/boneabs.5.P416

ECTS2016 Poster Presentations Osteoporosis: treatment (40 abstracts)

Hydrogen sulfide is a novel regulator of bone formation involved in the bone loss induced by estrogen deficiency

Laura Gambari 1 , Abdul Malik Tiagy 2 , Gina Lisignoli 1 , Roberto Pacifici 2 & Francesco Grassi 1


1Istituto Ortopedico Rizzoli, Lab RAMSES, Bologna, Italy; 2Division of Endocrinology, Metabolism and Lipids, Emory University, Atlanta, GA, USA.


Hydrogen sulfide (H2S) is a gaseous molecule produced endogenously in mammalian cells. H2S was recently found to play important roles in the regulation of inflammation, redox homeostasis and cell lifespan. Moreover, H2S was shown to maintain mesenchymal stem cell (MSC) function and stimulate osteogenic differentiation of MSC. However, it is unclear whether H2S plays any role in the bone loss induced by estrogen deficiency.

The objective of this study was to investigate the role of the endogenous pathway leading to H2S generation in ovariectomy (ovx)-induced bone loss in mice.

We found that ovx induced a 29% decrease in femural BV/TV relative to sham mice (P<0.0001). Moreover, ovx decreased serum H2S levels by 65% (P<0.001) and blunted the bone marrow (BM) mRNA expression of the two key H2S-generating enzymes (P<0.001), cystathione β-synthase (CBS) and cystathione γ-lyase (CSE). To restore H2S levels, mice were treated with a common H2S-donor drug, GYY4137 (GYY) (1 mg/mouse, every other day) for 4 weeks and indexes of bone mass were measured by μCT and hystomorphometry. We found that treatment with GYY normalizes serum H2S levels in ovx mice, and completely prevents the loss of femural BV/TV. Hystomorphometry revealed that GYY induced a significant increase in N.Ob-BS and Ob.S/BS (P<0.05). Furthermore, GYY-treated mice significantly increased serum levels of P1NP, a marker of bone formation, and increased CFU-ALP formation ex vivo by 28% relative to ovx mice (P<0.0001). Treatment with GYY resulted in increased WNT signaling in BMSCs and increased the expression of the WNT ligands Wnt16, Wnt2b, Wnt6 and Wnt10b in the BM. Experiments performed in human BM cells confirmed that H2S stimulates osteogenic differentiation of MSC. In summary, we show that ovx is associated with impaired H2S synthesis in mice, and that pharmacological replacement of H2S stimulates bone formation preventing the bone loss induced by estrogen deficiency.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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