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

人类分离骨细胞和克氏综合征中硬化蛋白与 INSL3 之间的负相关性:睾丸-骨串扰的新提示

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作者:Andrea Di Nisio, Luca De Toni, Maria Santa Rocca, Marco Ghezzi, Riccardo Selice, Giuseppe Taglialavoro, Alberto Ferlin, Carlo Foresta

Conclusions

We report 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.

Results

Sclerostin levels were significantly increased in KS subjects, and negatively correlated with INSL3 levels in both cohorts and with bone mineral density in the KS group. Stimulation of cultured osteocytes with INSL3 at 10-7 M significantly decreased both sclerostin messenger RNA and protein expression. Conclusions: We report 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.

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