The IL-23 receptor (IL-23R) signaling pathway has pleiotropic effects on the differentiation of osteoclasts and osteoblasts, since it can inhibit or stimulate these processes via different pathways. However, the potential role of this pathway in the regulation of bone homeostasis remains elusive. Therefore, we studied the role of IL-23R signaling in physiological bone remodeling using IL-23R deficient mice. Using µCT, we demonstrate that 7-week-old IL-23R-/- mice have similar bone mass as age matched littermate control mice. In contrast, 12-week-old IL-23R-/- mice have significantly lower trabecular and cortical bone mass, shorter femurs and more fragile bones. At the age of 26 weeks, there were no differences in trabecular bone mass and femur length, but most of cortical bone mass parameters remain significantly lower in IL-23R-/- mice. In vitro osteoclast differentiation and resorption capacity of 7- and 12-week-old IL-23R-/- mice are similar to WT. However, serum levels of the bone formation marker, PINP, are significantly lower in 12-week-old IL-23R-/- mice, but similar to WT at 7 and 26 weeks. Interestingly, Il23r gene expression was not detected in in vitro cultured osteoblasts, suggesting an indirect effect of IL-23R. In conclusion, IL-23R deficiency results in temporal and long-term changes in bone growth via regulation of bone formation.
We discuss the role of PINK1/PARKIN signalling in neurodegeneration and neuroinflammation. With a particular focus on its role in mitochondrial dysfunction in disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer ́s, Huntington ́s and Parkinson ́s diseases, as well as eye diseases such as age-related macular degeneration (AMD) and glaucoma.
|Author/s||Quinn PM, Buck TM, Mulder AA, Ohonin C, Alves CH, Vos RM, Bialecka M, van Herwaarden T, van Dijk EHC, Talib M, Freund C, Mikkers HMM, Hoeben RC, Goumans MJ, Boon CJF, Koster AJ, Chuva de Sousa Lopes SM, Jost CR, Wijnholds J|
|Journal||Stem Cell Reports, 2019 May 14;12(5):906-919|
|Comment||Manuscript describes a retinal phenotype in cultured human CRB1 patient iPSC-derived retinal organoids as previously detected in vivo in mice lacking retinal CRB1 or CRB2.|
Keywords: Crumbs homologue-1; Leber congenital amaurosis; Microglia; Retina; Retinal inflammation; Retinitis pigmentosa.
We have a new toy in the lab!
The optomotor response (OMR) is a reflex used to assess visual function. The PhenoSys qOMR (quantitative optomotor response) is a unique system that automatically measures the OMR with minimal experimenter effort. It uses a virtual stimulation cylinder that continuously aligns with the animal´s head position. Based on real-time head tracking, quantitative OMR measurements run fully automatically and objectively.
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For the first time, we demonstrate loss of functional vision in a mouse model for CRB1-retinitis pigmentosa.
@Vicentine Coast, Portugal, together with Bike&Beer BTT team (30-7-2019)
Picture by CH Alves