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Objective(s): Previous study has indicated that triiodothyronine (T3) facilitated cartilage degeneration in osteoarthritis (OA). This study aimed to investigate the effects of T3 on angiogenesis-related factor expression in human osteoblasts of OA subchondral bone.Materials and Methods: The subchondral bone specimens were obtained from OA patients and healthy participants. The expressions of VEGF, HIF-1α, AKT, and phosphorylated AKT was detected by immunohistochemistry, Western blotting, and RT-qPCR in OA. Angiogenesis-related factor expression in OA osteoblasts was measured by treating different concentrations of T3. The hypoxia model and PX-478 (HIF-1α inhibitor) were employed to confirm the regulative role of HIF-1α for VEGF expression. The level of VEGF secretion was examined in osteoblasts supernatant using ELISA. Results: Immunohistochemistry showed strong staining of VEGF and HIF-1α in OA subchondral bone. The expression of VEGF, HIF-1α, and p-AKT in OA osteoblasts was higher than that of normal osteoblasts at protein and mRNA levels. The physiological concentration of T3 (10-7 M) in OA osteoblasts up-regulated the expression of VEGF, HIF-1α, and p-AKT after 24 hr and 48 hr culture, while a higher dose of T3 displayed the adverse effects. Additionally, VEGF and p-AKT expression was down-regulated when PX-478 inhibited HIF-1α protein. Conclusion: Our results suggested that local T3 could effectively increase angiogenesis-related factor expression by PI3K/AKT signaling pathway, and HIF-1α regulated the VEGF expression in OA osteoblasts.

Previous studies suggested that tropical sea surface salinity (SSS) can influence tropical Pacific sea surface temperature (SST) through mixing and entrainment and thus it may be a signal for El Niño‐Southern Oscillation (ENSO) prediction. This paper explores the influence of SSS on ENSO spring predictability barrier (SPB) using an empirical dynamic model ‐ Linear Inverse Model (LIM). By coupling and decoupling SSS in the LIM, we find that tropical Pacific SSS plays a significant role in weakening both Central‐Pacific and Eastern‐Pacific ENSO SPB. The evolution of optimal initial structure also shows the importance of SSS dynamics in ENSO. We found an SSS mode that plays the dominant role in SSS impacting ENSO prediction. By the analysis of lead‐lag correlation, we find that this mode can induce easterlies during the spring, which finally leads to a La Niña‐like SST pattern in the winter through zonal advective and thermocline feedbacks. Plain Language Summary: The spring predictability barrier (SPB) is a phenomenon of forecast skill reduction of the El Niño‐Southern Oscillation (ENSO) when it comes to the boreal spring, regardless of the initial month. Sea surface salinity (SSS) can influence sea surface temperature by altering sea surface density and thus it may be a signal for ENSO prediction. Using a linear dynamical model, we find that SSS plays an important role in improving the forecast skill of ENSO and weakening SPB. We further find that SSS can induce the easterlies during the spring, which finally leads to a La Niña‐like SST pattern. Our study suggests that SSS can be used to predict ENSO about 1 year later. Key Points: A linear dynamical model suggests that taking sea surface salinity (SSS) into consideration can strongly weaken Central‐Pacific and Eastern‐Pacific El Niño‐Southern Oscillation (ENSO) spring predictability barrier (SPB)A new SSS mode is found to be important for weakening ENSO SPBThe SSS mode can predict ENSO events about 1 year earlier by inducing sea surface temperature and wind anomalies in the early spring [ABSTRACT FROM AUTHOR]