Axon to dendrite connectivity12/25/2023 ![]() ![]() While the characteristics and functions of the lacunar-canalicular network (LCN) have been recently reviewed, the specific role of dendrites and dendrite-dendrite connectivity has received less attention. In addition to the dramatic cellular morphological transition associated with osteocyte maturation, osteocytes acquire distinct and novel functions to control bone strength compared to osteoblasts, including (1) regulating bone remodeling by producing paracrine-acting factors, (2) mechanosensing, and (3) maintaining mineral homeostasis. Osteoblasts are cuboidal cells with abundant rough endoplasmic reticulum (ER) in contrast, osteocytes possess cigar-shaped nuclei, scant ER, and large numbers of long, branching dendrites. Following the deposition of calcium and phosphate along collagen fibrils, mature osteocytes are eventually formed by the integration of new dendrites into the existing osteocyte dendrite network. Osteoblasts that will become osteocytes are first surrounded by the unmineralized collagenous matrix they have produced (osteoid) next, developing osteocytes initiate dendrite formation prior to matrix mineralization. The mechanisms of how some osteoblasts differentiate into osteocytes remain incompletely understood. Surrounded by mineralized matrix, osteocytes possess an elaborate network of dendrite-like connections that are used for mechanosensing and inter-cellular communication. Osteocytes are the most abundant and longest-lived cells in bone. Future therapeutic approaches are needed to target the process of osteocyte dendrite formation.īone-forming osteoblasts can undergo one of at least three fates: death by apoptosis, formation of bone lining cells, and differentiation into osteocytes. Recent advances in multi-omics, in vivo and in vitro models, and microscopy-based imaging have provided novel approaches to reveal the underlying mechanisms that regulate dendrite development. This review addresses the impact of osteocyte dendrites in bone health and disease. ![]() A few mechanisms are proposed to control dendrite formation and outgrowth, such as via the regulation of actin polymerization dynamics. It is suggested that there is a causal relationship between the loss of osteocyte dendrites and the increased osteocyte apoptosis during conditions including aging, microdamage, and skeletal disease. The purpose of this review is to discuss the molecular mechanisms involved in osteocyte dendrite formation, summarize the similarities between osteocytic and neuronal projections, and highlight the importance of osteocyte dendrite maintenance in human skeletal disease. ![]()
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