Sclerostin, the protein product of the Sost gene, is a potent inhibitor of bone formation. Among bone cells, sclerostin is found nearly exclusively in the osteocytes, the cell type that historically has been implicated in sensing and initiating mechanical signaling. The recent discovery of the antagonistic effects of sclerostin on Lrp5 receptor signaling, a crucial mediator of skeletal mechanot...

The strong correlation between a bone's architectural properties and the mechanical forces that it experiences has long been attributed to the existence of a cell that not only detects mechanical load but also structurally adapts the bone matrix to counter it. One of the most likely cellular candidates for such a "mechanostat" is the osteocyte, which resides within the mineralized bone matrix a...

Osteocytes are bone cells that can sense mechanical cues (stress and strain) respond by releasing biochemical signals direct remodeling. This process is called mechanotransduction which, in osteocytes, not well understood yet because vivo studies have proven difficult due to the complexity inaccessibility of flow–osteocyte lacuna-canaliculi system. While silico (modeling simulation) become powe...

Mechanical loading, a potent stimulator of bone formation, is governed by osteocyte regulation of osteoblasts. We developed a three-dimensional (3D) in vitro co-culture system to investigate the effect of loading on osteocyte-osteoblast interactions. MLO-Y4 cells were embedded in type I collagen gels and MC3T3-E1(14) or MG63 cells layered on top. Ethidium homodimer staining of 3D co-cultures sh...

Osteocytes are well evidenced to be the major mechanosensor in bone, responsible for sending signals to the effector cells (osteoblasts and osteoclasts) that carry out bone formation and resorption. Consistent with this hypothesis, it has been shown that osteocytes release various soluble factors (e.g. transforming growth factor-beta, nitric oxide, and prostaglandins) that influence osteoblasti...

Osteocytes, regarded as the mechanical sensor in bone, respond to mechanical stimulation by activating biochemical pathways and mediating the cellular activities of other bone cells. Little is known about how osteocytic networks respond to physiological mechanical stimuli. In this study, we compared the mechanical sensitivity of osteocytic and osteoblastic networks under physiological-related f...

Mutations in WNT1 cause osteogenesis imperfecta (OI) and early-onset osteoporosis, identifying it as a key Wnt ligand in human bone homeostasis. However, how and where WNT1 acts in bone are unclear. To address this mechanism, we generated late-osteoblast-specific and osteocyte-specific WNT1 loss- and gain-of-function mouse models. Deletion of Wnt1 in osteocytes resulted in low bone mass with sp...

A human mission to Mars will be physically demanding and presents a variety of medical risks to crewmembers. It has been recognized for over a century that loading is fundamental for bone health, and that reduced loading, as in prolonged bed rest or space flight, leads to bone loss. Osteocytes, the most abundant bone cell type, are thought to be key mechanical sensors in bone, yet the molecular...

The sexual dimorphism in age-related loss of human vertebral cancellous bone is not fully understood and could be related to dimorphism in the bone cell populations. The objective of this study was to investigate age- and gender-related differences in the osteocyte population and its relationship with bone volume fraction for human vertebral cancellous bone. Histomorphometric techniques were us...

Signaling molecules produced by osteocytes have been proposed to serve as soluble factors that contribute to bone remodeling, as well as to homeostasis of other organs. However, to the best of our knowledge, there are currently no studies investigating the role of osteocyte-secreted exosomes. In the present study, ablation of osteocytes in mice [osteocyte-less (OL)] was used to examine the micr...