Correction: Xiong, Z., et al. Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development. Int. J. Mol. Sci. 2015, 16, 21153–21176

The authors wish to replace Figure 4A on Page 21161 of their paper published in IJMS [1]. [...

Different Roles of GRP78 on Cell Proliferation and Apoptosis in Cartilage Development

Eukaryotic cells possess several mechanisms to adapt to endoplasmic reticulum (ER) stress and thereby survive. ER stress activates a set of signaling pathways collectively termed as the unfolded protein response (UPR). We previously reported that Bone morphogenetic protein 2 (BMP2) mediates mild ER stress and activates UPR signal molecules in chondrogenesis. The mammalian UPR protects the cell against the stress of misfolded proteins in the endoplasmic reticulum. Failure to adapt to ER stress causes the UPR to trigger apoptosis. Glucose regulated protein 78 (GRP78), as an important molecular chaperone in UPR signaling pathways, is responsible for binding to misfolded or unfolded protein during ER stress. However the influence on GRP78 in BMP2-induced chondrocyte differentiation has not yet been elucidated and the molecular mechanism underlyng these processes remain unexplored. Herein we demonstrate that overexpression of GRP78 enhanced cell proliferation in chondrocyte development with G1 phase advance, S phase increasing and G2-M phase transition. Furthermore, overexpression of GRP78 inhibited ER stress-mediated apoptosis and then reduced apoptosis in chondrogenesis induced by BMP2, as assayed by cleaved caspase3, caspase12, C/EBP homologous protein (CHOP/DDIT3/GADD153), p-JNK (phosphorylated c-Jun N-terminal kinase) expression during the course of chondrocyte differentiation by Western blot. In addition, flow cytometry (FCM) assay, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling (TUNEL) assay and immune-histochemistry analysis also proved this result in vitro and in vivo. It was demonstrated that GRP78 knockdown via siRNA activated the ER stress-specific caspase cascade in developing chondrocyte tissue. Collectively, these findings reveal a novel critical role of GRP78 in regulating ER stress-mediated apoptosis in cartilage development and the molecular mechanisms involved

Influence of Seasonal Air–Sea Interaction on the Interannual Variation of the NPP of Terrestrial Natural Vegetation in China

Based on Moderate Resolution Imaging Spectoradiometer (MODIS) remote sensing data, meteorological observation data, multisource atmospheric circulation, and sea surface temperature (SST) data from NCEP/NCAR reanalysis, we estimated the net primary productivity (NPP) of terrestrial natural vegetation in China according to the CASA model and analyzed the linear trend and interannual fluctuation of NPP, as well as the spatial distribution characteristics of the annual NPP response to climatic factors. The obtained results revealed the impact of air–sea interaction on interannual NPP variability in key climatic areas. In China, the annual NPP of natural vegetation, linear NPP trend, and interannual NPP fluctuation showed significant regional characteristics. The annual NPP exhibited a significant increasing trend and interannual fluctuation in North China and Northeast China, with spatially consistent responses from NPP to precipitation and temperature. On the seasonal time scale, NPP in the key climatic area (105~135° E, 35~55° N) exhibited a strong response to both summer precipitation and mean temperature. In the summer atmospheric circulation, the circulation anomaly area is mainly distributed in the northeast cold vortex area in the middle- and high-latitude westerlies in East Asia and in the Sea of Okhotsk with dipole circulation. In the SST of the preceding winter and spring, the key SST anomaly area was the Kuroshio region, with an impact of the Kuroshio SST anomaly on the interannual variation in annual NPP in the key climatic area. The cold vortex in Northeast China played a pivotal role in the influence of the SST anomaly in the Kuroshio region on atmospheric circulation anomalies, resulting in abnormal summer precipitation in the key climatic region and affecting the annual accumulation of NPP of natural vegetation

Gut-joint axis: Oral Probiotic ameliorates Osteoarthritis

Osteoarthritis (OA) etiology is multifactorial, and its prevalence is growing globally. The Gut microbiota shapes our immune system and impacts all aspects of health and disease. The idea of utilizing probiotics to treat different conditions prevails. Concerning musculoskeletal illness and health, current data lack the link to understand the interactions between the host and microbiome. We report that S. thermophilus, L. pentosus (as probiotics), and γ-aminobutyric acid (GABA) harbour against osteoarthritis in vivo and alleviate IL-1β induced changes in chondrocytes in vitro. We examined the increased GABA concentration in mice's serum and small intestine content followed by bacterial treatment. The treatment inhibited the catabolism of cartilage and rescued mice joints from degradation. Furthermore, the anabolic markers upregulated and decreased inflammatory markers in mice knee joints and chondrocytes. This study is the first to represent GABA's chondrogenic and chondroprotective effects on joints and human chondrocytes. This data provides a foundation for future studies to elucidate the role of GABA in regulating chondrocyte cell proliferation. These findings opened future horizons to understanding the gut-joint axis and OA treatment. Thus, probiotic/GABA therapy shields OA joints in mice and could at least serve as adjuvant therapy to treat osteoarthritis