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Tibial bone compression promotes recovery after brain injury through osteocyte PIEZO1.

Traumatic brain injury (TBI) accelerates bone healing and induces heterotopic ossification, raising the question of whether an injured brain benefits from bone. Here we reveal that dynamic compressive tibial axial loading (DCTAL), a model of tibial bone compression, increased survival and promoted motor and cognitive recovery after stroke and TBI in mice, as well as in pig TBI models. DCTAL reduced neuron loss, attenuated chronic inflammation and astrogliosis and stimulated neuronal regeneration after TBI. Deletion of the mechanosensory channel Piezo1 in osteocytes reversed these benefits, whi…

Роман CCL3-HMGB1 Ось сигнала регулирует выражение остеоцита РАНКЛ в множестве миеломы.

Множественная миелома (ММ) — клональная плазменная клетка, вызывающая изнурительное заболевание костей. Остеолитическое разрушение, которое является отличительной чертой MM, вызвано увеличением остеокластного числа и усилившейся ресорбцией костей, главным образом в результате чрезмерного производства RANKL, главного регулятора образования остеокласта, в пределах ниши опухоли. Ранее мы сообщали, что остеоциты, самые изобилие клеток в костной нише, поощряют прогрессию опухоли и поддерживают болезнь костей MM, перепроизводяя RANKL. Однако молекулярные механизмы, лежащие в основе регулирования РАН

Совпадение в аннотации оригинала
Multiple myeloma (MM) is a clonal plasma cell proliferative malignancy characterized by a debilitating bone disease. Osteolytic destruction, … , the master regulator of osteoclast formation, within the tumor niche. We previously reported that osteocytes, the most abundant cells in the bone niche, promote tumor progression and support MM bone disease by overproducing RANKL. However, the molecular mechanisms underlying RANKL dysregulation in osteocytes in the context of MM bone disease are not entire …

Nanocrystal Compressive Residual Stresses: A Strategy to Strengthen the Bony Spines of Osteocytic and Anosteocytic Fish.

Bone is a living tissue in which communicating cells, osteocytes, are assumed to be vital for tissue turnover and adaptation. Interestingly however, most advanced teleost fish do not possess osteocyte-mediated porosity, prompting intriguing questions about alternative material-strategies for these bones to cope with damage. Using advanced imaging techniques, including phase-contrast enhanced (PCE) microtomography (µCT) and nanotomography (nanoCT), X-ray fluorescence (XRF), and diffraction (XRD) tomography, the micro- and nano-architectures of osteocytic zebrafish are compared with anosteocytic…

Osteocytic FSH inhibition rescues bone mass and boosts fracture healing in ovariectomized mice.

AIMS: Postmenopausal osteoporosis significantly increases fragility fracture risk. While menopausal estrogen decline coincides with rising f … ated callus maturation and improved biomechanical healing post-fracture. SIGNIFICANCE: We identify osteocytes as direct FSH target cells. Osteocyte Fshr deletion promotes bone turnover and accelerates fracture repair in ovariectomized mice by enhancing PI3K/Akt signaling. These findings reveal a new pathophysiological mechanism for postmenopausal osteoporos …

Osteocytic vinculin controls bone mass by modulating Mef2c-driven sclerostin expression in mice.

The focal adhesion (FA) is the structural basis of the cell-extracellular matrix crosstalk and plays important roles in control of organ formation and function. Here we show that expression of FA protein vinculin is dramatically reduced in osteocytes in patients with aging-related osteoporosis. Vinculin loss severely impaired osteocyte adhesion and dendrite formation. Deleting vinculin using the mouse 10-kb Dmp1-Cre transgenic mice causes dramatic bone loss in the weight-bearing long bones and spine, but not in the skull, in both young and aged mice by impairing osteoblast formation and functi…

Suppression of apoptosis in osteocytes, the potential way of natural medicine in the treatment of osteonecrosis of the femoral head.

OBJECTIVES: In the field of orthopedics, osteonecrosis of the femoral head (ONFH) is a common and refractory condition sometimes known as "immortal cancer" due to its complicated etiology, difficult treatment, and high disability rate. This paper's main goal is to examine the most recent literature on the pro-apoptotic effects of traditional Chinese medicine TCM monomers or compounds on osteocytes and to provide a summary of the potential signal routes. METHODS: The last ten years' worth of literature on ONFH as well as the anti-ONFH effects of aqueous extracts and monomers from traditional C…

The Protective Effects of Osteocyte-Derived Extracellular Vesicles Against Alzheimer's Disease Diminished with Aging.

Both Alzheimer's disease (AD) and osteoporosis (OP) are common age-associated degenerative diseases and are strongly correlated with clinical epidemiology. However, there is a lack of clear pathological relationship between the brain and bone in the current understanding. Here, it is found that young osteocyte, the most abundant cells in bone, secretes extracellular vesicles (OCYYoung -EVs) to ameliorate cognitive impairment and the pathogenesis of AD in APP/PS1 mice and model cells. These benefits of OCYYoung -EVs are diminished in aged osteocyte-derived EVs (OCYAged -EVs). Based on the self-

Inhibition of the Growth of Breast Cancer-Associated Brain Tumors by the Osteocyte-Derived Conditioned Medium.

The brain is a common site of metastasis from advanced breast cancer but few effective treatments are available. We examined a therapeutic option with a conditioned medium (CM), focusing on the role of Lrp5 and β-catenin in Wnt signaling, and IL1ra in osteocytes. Osteocytes presented the innate anti-tumor effect and the overexpression of the above genes strengthened their action. In a mouse model, the injection of their CM inhibited mammary tumors and tumor-driven osteolysis. Importantly, Lrp5- and/or IL1ra-overexpressing osteocytes or the local administration of β-catenin-overexpressing CM ma…

Endoplasmic reticulum stress mediates osteocyte death under oxygen-glucose deprivation in vitro.

UNLABELLED: As a vascularized organ, bone is known to be susceptible to ischemia. Ischemic osteonecrosis or skeletal unloading lead to ischemia in bone microenvironment that causes osteocytes to suffer hypoxia and nutrition deprivation. OBJECTIVE: To explore the effects of Oxygen-glucose deprivation (OGD) on osteocytes and the potential mechanism. METHODS: OGD model was established in cultured MLO-Y4 cell. Cell damage, intracellular oxidative stress and cell apoptosis were detected at different OGD times (0, 2, 4, 8, 12, 24 h), and the changes in endoplasmic reticulum (ER) stress-related ind…

HIF-1α facilitates osteocyte-mediated osteoclastogenesis by activating JAK2/STAT3 pathway in vitro.

Osteocytes, entrapped within the mineralized bone matrix, has been found to have numerous functions such as acting as an orchestrator of bone remodeling through regulation of both osteoclast and osteoblast activity and also functioning as an endocrine cell. Due to a specialized morphology and surrounding structure, osteocytes are more tolerant to hypoxia during osteoporosis, fracture, osteoarthritis, and orthodontic-orthognathic combination therapy. Hypoxia-inducible factor-1α (HIF-1α) is one of the master regulators of hypoxia reactions, playing an important role in bone modeling, remodeling,…

Bone Regulates Browning and Energy Metabolism Through Mature Osteoblast/Osteocyte PPARγ Expression.

Peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of energy metabolism. In bone, it is known to regulate osteoblast differentiation and osteoclast activity. Whether PPARγ expression in bone cells, particularly osteocytes, regulates energy metabolism remains unknown. Here, we show that mature osteoblast/osteocyte-specific ablation of PPARγ in mice (Ocy-PPARγ-/-) alters body composition with age, namely, to produce less fat and more lean mass, and enhances insulin sensitivity and energy expenditure compared with wild-type mice. In addition, Ocy-PPARγ-/- mice exhibit more…

Autocrine and Paracrine Regulation of the Murine Skeleton by Osteocyte-Derived Parathyroid Hormone-Related Protein.

Parathyroid hormone-related protein (PTHrP) and parathyroid hormone (PTH) have N-terminal domains that bind a common receptor, PTHR1. N-terminal PTH (teriparatide) and now a modified N-terminal PTHrP (abaloparatide) are US Food and Drug Administration (FDA)-approved therapies for osteoporosis. In physiology, PTHrP does not normally circulate at significant levels, but acts locally, and osteocytes, cells residing within the bone matrix, express both PTHrP and the PTHR1. Because PTHR1 in osteocytes is required for normal bone resorption, we determined how osteocyte-derived PTHrP influences the s…

Excessive Osteocytic Fgf23 Secretion Contributes to Pyrophosphate Accumulation and Mineralization Defect in Hyp Mice.

X-linked hypophosphatemia (XLH) is the most frequent form of inherited rickets in humans caused by mutations in the phosphate-regulating gen … u mRNA expression profiling in bone cryosections revealed a ~70-fold up-regulation of Fgfr3 mRNA in osteocytes versus osteoblasts of Hyp mice. In addition, we show that blocking of increased Fgf23-FGFR3 signaling with anti-Fgf23 antibodies or an FGFR3 inhibitor partially restored the suppression of Tnap expression, phosphate production, and mineralization, a …

Strain amplification analysis of an osteocyte under static and cyclic loading: a finite element study.

Osteocytes, the major type of bone cells which reside in their lacunar and canalicular system within the bone matrix, function as biomechanosensors and biomechanotransducers of the bone. Although biomechanical behaviour of the osteocyte-lacunar-canalicular system has been investigated in previous studies mostly using computational 2-dimensional (2D) geometric models, only a few studies have used the 3-dimensional (3D) finite element (FE) model. In the current study, a 3D FE model was used to predict the responses of strain distributions of osteocyte-lacunar-canalicular system analyzed under st…

Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy.

BACKGROUND: Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. METHODS: Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35-Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period…

Increased osteocyte death in multiple myeloma patients: role in myeloma-induced osteoclast formation.

The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast (OCL) formation and bone lesions is still unknown. Osteocytes regulate bone remodelling at least partially, as a result of their cell death triggering OCL recruitment. In this study, we found that the number of viable osteocytes was significantly smaller in MM patients than in healthy controls, and negatively correlated with the number of OCLs. Moreover, the MM patients with bone lesions had a significantly smaller number of viable osteocytes than those without, partly because of increased apoptosis. These findings were …

Immunolocalization of sclerostin synthesized by osteocytes in relation to bone remodeling in the interradicular septa of ovariectomized rats.

This study aimed at elucidating whether estrogen deficiency would affect the synthesis of an osteocyte-derived factor, sclerostin, in the mesial region of alveolar bone. Eight 9-week-old Wistar female rats were ovariectomized (OVX) and eight other rats were Sham-operated (Sham). After 4 weeks, the interradicular septa of mandibular first molar were embedded in paraffin and then histochemically examined. Sclerostin-positive osteocytes were located in the superficial layer of the mesial region of Sham bones, whereas the OVX mesial region showed less sclerostin-reactive osteocytes. There was no s…

The osteocyte in CKD: new concepts regarding the role of FGF23 in mineral metabolism and systemic complications.

The identification of elevated circulating levels of the osteocytic protein fibroblast growth factor 23 (FGF23) in patients with chronic kidney disease (CKD), along with recent data linking these values to the pathogenesis of secondary hyperparathyroidism and to systemic complications, has changed the approach to the pathophysiology and treatment of disordered bone and mineral metabolism in renal failure. It now appears that osteocyte biology is altered very early in the course of CKD and these changes have implications for bone biology, as well as for progressive cardiovascular and renal dise

Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy.

Chronic kidney disease-mineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric … in was observed both in mouse and human bones. Overall repression of Wnt/β-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-κB ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) rati …

Estrogen withdrawal alters cytoskeletal and primary ciliary dynamics resulting in increased Hedgehog and osteoclastogenic paracrine signalling in osteocytes.

Estrogen deficiency during post-menopausal osteoporosis leads to osteoclastogenesis and bone loss. Increased pro-osteoclastogenic signalling (RANKL/OPG) by osteocytes occurs following estrogen withdrawal (EW) and is associated with impaired focal adhesions (FAs) and a disrupted actin cytoskeleton. RANKL production is mediated by Hedgehog signalling in osteocytes, a signalling pathway associated with the primary cilium, and the ciliary structure is tightly coupled to the cytoskeleton. Therefore, the objective of this study was to investigate the role of the cilium and associated signalling in E…