Negative Association Between Sclerostin and INSL3 in Isolated Human Osteocytes and in Klinefelter Syndrome: New Hints for Testis-Bone Crosstalk.

Negative Association Between Sclerostin and INSL3 in Isolated Human Osteocytes and in Klinefelter Syndrome: New Hints for Testis-Bone Crosstalk.

J Clin Endocrinol Metab. 2018 Feb 14;:

Authors: Di Nisio A, De Toni L, Rocca MS, Ghezzi M, Selice R, Taglialavoro G, Ferlin A, Foresta C

Abstract
Context/Objective: The regulation of bone mass by the testis is a well-recognized mechanism, but the role of Leydig-specific marker insuline-like 3 peptide (INSL3) on the most abundant bone cell population, osteocytes, is unknown. In this study we aimed to investigate the relationship between INSL3 and Sclerostin, an osteocyte-specific protein that negatively regulates bone formation.
Design/Setting: Serum sclerostin and INSL3 levels were evaluated in Klinefelter Syndrome (KS) and healthy controls. In vitro effect of INSL3 on sclerostin production was evaluated in human cultured osteocytes.
Patients: 103 KS patients and 60 age- and gender-matched controls were recruited.
Main outcome measures: Serum sclerostin and INSL3 levels were assessed by enzyme-linked immunosorbent assay. Osteocytes were isolated by fluorescence-assisted cell sorting. Sclerostin expression was evaluated by western blot, immunofluorescence and RT-PCR. Measurement of bone mineral density (BMD) was done by dualenergy X-ray absorptiometry (DEXA) at lumbar spine (L1-L4) and femoral neck (FN).
Results: Sclerostin levels were significantly increased in KS subjects, and negatively correlated with INSL3 levels in both cohorts and with BMD in KS group. Stimulation of cultured osteocytes with INSL3 at 10-7 M significantly decreased both SOST mRNA and protein expression.
Conclusions: We report for the first time a negative association between the testicular hormone INSL3 and the osteocytic negative regulator of bone formation, sclerostin. We further explored this association in vitro, and showed that INSL3 was able to reduce sclerostin expression. These results add further knowledge on the emerging role of sclerostin as a therapeutic target for osteoporosis treatment.

PMID: 29452406 [PubMed - as supplied by publisher]

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