Osteoprotegerin levels in children with subclinical hypothyroidism.

AIM: In this study, we investigated the osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappa Β ligand (sRANKL) serum levels in association with thyroid function in children with subclinical hypothyroidism. METHODS: In 143 children and adolescents with subclinical hypothyroidism and 343 with normal thyroid function, age, height, weight and pubertal status were recorded and TSH, free thyroxine (FT4), anti-thyroid antibodies, OPG and sRANKL were measured in serum. Multiple linear regression was used for the statistical analysis with P < .05. RESULTS: Children with subclinical hypothyroidism had higher TSH and lower FT4 serum levels than the control group (P < .05). Both groups had similar BMI Z-score, OPG and sRANKL serum levels. After multiple regression analysis, in children with subclinical hypothyroidism, OPG was negatively associated with FT4 (P < .05) whilst no association was observed between OPG and sRANKL, as well as between FT4 serum levels and RANKL. CONCLUSION: Osteoprotegerin levels in children with subclinical hypothyroidism do not differ from those of euthyroid children. However, there is a negative association between FT4 and OPG levels observed only in the SH group. Considering the link between vascular dysfunction and alterations in osteoprotegerin levels, further research is needed to establish the role of childhood subclinical hypothyroidism in the long-term cardiovascular risk.

Coordinated activation of TGF-ß and BMP pathways promotes autophagy and limits liver injury after acetaminophen intoxication.

Ligands of the transforming growth factor-ß (TGF-ß) superfamily, including TGF-ßs, activins, and bone morphogenetic proteins (BMPs), have been implicated in hepatic development, homeostasis, and pathophysiology. We explored the mechanisms by which hepatocytes decode and integrate injury-induced signaling from TGF-ßs and activins (TGF-ß/Activin) and BMPs. We mapped the spatiotemporal patterns of pathway activation during liver injury induced by acetaminophen (APAP) in dual reporter mice carrying a fluorescent reporter of TGF-ß/Activin signaling and a fluorescent reporter of BMP signaling. APAP intoxication induced the expression of both reporters in a zone of cells near areas of tissue damage, which showed an increase in autophagy and demarcated the borders between healthy and injured tissues. Inhibition of TGF-ß superfamily signaling by overexpressing the inhibitor Smad7 exacerbated acute liver histopathology but eventually accelerated tissue recovery. Transcriptomic analysis identified autophagy as a process stimulated by TGF-ß1 and BMP4 in hepatocytes, with Trp53inp2, which encodes a rate-limiting factor for autophagy initiation, as the most highly induced autophagy-related gene. Collectively, these findings illustrate the functional interconnectivity of the TGF-ß superfamily signaling system, implicate the coordinated activation of TGF-ß/Activin and BMP pathways in balancing tissue reparatory and regenerative processes upon APAP-induced hepatotoxicity, and highlight opportunities and potential risks associated with targeting this signaling system for treating hepatic diseases.