![]() ![]() Recent estimates suggest that the osteocyte connectivity network in human bone exhibits the same order of complexity as the network of connections between neurons in the brain 9. Defects in the osteocyte dendrite network may cause skeletal fragility in the setting of aging and glucocorticoid treatment 7, 8. The osteocyte dendritic network confers mechano-sensitivity to these cells and allows for extensive communication among osteocytes and adjacent cells on bone surfaces 6. Furthermore, osteocytes have a unique morphology as they bear multiple long, neuron-like dendritic processes projecting through the lacunar canalicular system in bone 5. These cells translate external cues, such as hormonal variations and mechanical stresses, into changes in bone remodeling by secreting paracrine-acting factors that regulate osteoblast and osteoclast activity 4. Recently, emerging evidence has highlighted key roles for osteocytes in bone remodeling 3. Although the roles of osteoblasts and osteoclasts in bone formation and resorption have been well studied 1, 2, those of osteocytes, the most abundant cell type in bone, had been overlooked due to technological limitations and the cells’ relatively inaccessible location within the mineralized bone matrix. The major cell types that govern bone homeostasis are osteoblasts, osteoclasts, and osteocytes. These findings reveal a role for Sp7 and its target gene Osteocrin in osteocytogenesis, revealing that pathways that control osteocyte development influence human bone diseases. Sp7-dependent genes that mark osteocytes are enriched in neurons, highlighting shared features between osteocytic and neuronal connectivity. Moreover, humans with a SP7 R316C mutation show defective osteocyte morphology. Sp7-dependent osteocyte gene networks are associated with human skeletal diseases. Single-cell RNA-sequencing demonstrates defects in osteocyte maturation in the absence of Sp7. Osteocrin is a Sp7 target gene that promotes osteocyte dendrite formation and rescues defects in Sp7-deficient mice. Profiling of Sp7 target genes and binding sites reveals unexpected repurposing of this transcription factor to drive dendrite formation. Here we show that deletion of Sp7 in osteoblasts and osteocytes causes defects in osteocyte dendrites. The circuitry that drives dendrite formation during “osteocytogenesis” is poorly understood. Some osteoblasts embed within bone matrix, change shape, and become dendrite-bearing osteocytes. ![]() ![]() Nature Communications volume 12, Article number: 6271 ( 2021) Despite being able to join, when just trying to peek I always get either the never-ending "loading" spinner or "this room can't be previewed" message.Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin *) For some reason, previews never worked for me. I remember waiting for no less than 10 minutes in a similar scenario, and it used to consume nearly 100% of CPU available. Still a huge improvement over what it used to be. But seeing the most recent messages* and having an impression of joining the room should be nearly instantaneous. It could take a long while loading user pictures, presence states, ancient chat history and extra fluff. I get it that there are over 12k people in there, but I haven't seen any other platforms having similar issues.Īnd this just doesn't feel right, design-wise. Took me a two attempts and a couple minutes (!) to join a relatively crowded room at #synapse: on a freshly installed Synapse. While there's definitely lots of improvement, it's still painfully slow and eats lots (like, 40% of 1 core) of CPU time. I've just tried it again a week ago (last time was ~2 years ago). ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |