Disease relevance of Osteocytes

• In vitro experiments were performed to determine if OPN expression was altered in MLO-Y4 osteocytes by direct hypoxia (3, 6, 24, and 48 h) or hypoxia (3 and 24 h) followed by 24 h of reoxygenation [1].
• Biopsy specimens in the placebo and raloxifene groups had the appearance of normal bone, with no evidence of marrow fibrosis or increases in the amount of woven bone or numbers of empty osteocyte lacunae [2].
• Apoptosis of osteocytes in glucocorticoid-induced osteonecrosis of the hip [3].
• The purpose of this study was to observe the process of ischemia in osteocytes using light and electron microscopy and to compare the changes in these ischemic osteocytes with those in other types of osteocytes (i.e., degenerative osteocytes in physiological states, steroid-induced lipid-accumulating osteocytes) that have been previously reported [4].
• This suggests that osteocytes secrete significant amounts of TGF-beta, which inhibits bone resorption and is modulated by estrogen [5].

High impact information on Osteocytes

• We show here that SOST/sclerostin is expressed exclusively by osteocytes in mouse and human bone and inhibits the differentiation and mineralization of murine preosteoblastic cells (KS483) [6].
• Thus, failure of collagenase cleavage of type I collagen in Col1a1(r/r) mice is associated with osteocyte/osteoblast death but increases bone deposition in a manner that mimics the parathyroid hormone-induced bone surface activation seen in wild-type mice [7].
• Osteocyte perilacunar matrices stained with Ab that recognizes collagenase collagen alpha1(I) chain cleavage ends in wild-type but not Col1a1(r/r) calvariae [7].
• In hematoxylin and eosin-stained paraffin sections, we detect empty lacunae in osteocytes in calvariae from Col1a1(r/r) mice at age 2 weeks, increasing through age 10-12 months [7].
• Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition [8].

Chemical compound and disease context of Osteocytes

• The dead cell stain Ethidium homodimer-1 was used to tag dead osteocytes immediately after occlusion and produced a measure designated "osteonecrosis index." To detect leukocytes adhering to vessel walls, carboxyfluorescein diacetate, succinimidyl ester was injected at occluder release [9].
• The release of bone calcium and the resulting hypercalcemia in vitamin D3 toxicosis is therefore due to a direct toxic effect of the vitamin, or its metabolites, on the osteocyte resulting in osteonecrosis [10].

Biological context of Osteocytes

• We found that estrogen did not significantly reduce the proportion of osteocytes that were induced by mechanical stimulation to express c-fos and IGF-I mRNA; and estrogen suppressed mechanically induced osteogenesis whether administration was started 24 h before or 24 h after loading [11].
• Strong expression in osteocytes suggested that sclerostin expressed by these central regulatory cells mediates bone homeostasis [12].
• Upregulation of osteopontin by osteocytes deprived of mechanical loading or oxygen [1].
• Spatial distribution of Bax and Bcl-2 in osteocytes after bone fatigue: complementary roles in bone remodeling regulation [13]?
• Compared with the stretched osteocytes, which use stretch-activated and parathyroid hormone (PTH)-potentiated Ca2+ influx as an entry route to the protein kinase A (PKA) signal transduction pathways, there was no evidence of Ca2+ internalization by any of the cells tested on exposure to the ultrasound [14].

Anatomical context of Osteocytes

• The diffusion of fluorescein in bone is also consistent with the presence of an osteocyte pericellular matrix whose structure resembles that proposed for the endothelial glycocalyx [Squire, J. M., Chew, M., Nneji, G., Neal, C., Barry, J. & Michel, C. (2001) J. Struct. Biol. 136, 239-255] [15].
• Fetal blood MSCs cultured in adipogenic, osteogenic, or chondrogenic media differentiated, respectively, into adipocytes, osteocytes, and chondrocytes [16].
• The cellular alterations were characterized by multiple membrane-limited cytoplasmic vacuoles as seen for instance in liver, exocrine pancreas, kidney, thyroid gland, smooth muscle cells, osteocytes and in various neurons of the central and peripheral nervous systems [17].
• Dichloromethylene diphosphonate (Cl2MDP) antagonized the action of vitamin D on bone in thyroparathyroidectomized rats by reducing the metabolic activity of osteoblasts and osteocytes and decreasing the number of osteoclasts [18].
• Effects of mechanical strain on the function of Gap junctions in osteocytes are mediated through the prostaglandin EP2 receptor [19].

Associations of Osteocytes with chemical compounds

• These studies suggest that the EP2 receptor mediates the effects of autocrine PGE2 on the osteocyte gap junction in response to fluid flow-induced shear stress [19].
• However,the pericellular space of some osteocytes in rats given 5 units of 1,25-(OH)2D3 contained electron-dense granular deposits that were interpreted to be calcium phosphate [20].
• Cortisol at both dose levels failed to alter the electron microscopic appearance of osteoblasts, osteocytes, and osteoclasts with or without vitamin D. Bone turnover indicated by urinary hydroxyproline excretion was unaffected by cortisol treatment [21].
• Nitric oxide is one of the signaling molecules that is released upon mechanical stimulation of osteocytes and osteoblasts [22].
• Conversely, prolongation of ERK activation in osteocytes, by means of leptomycin B-induced inhibition of ERK export from the nucleus or overexpression of a green fluorescent protein-ERK2 mutant that resides permanently in the nucleus, converted the anti-apoptotic effect of 17beta-estradiol to a pro-apoptotic one [23].

Gene context of Osteocytes

• Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is mechanically responsive [24].
• Immunohistochemistry on adult mouse bone showed osteocrin localization in osteoblasts and young osteocytes [25].
• Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo [26].
• These data indicate that Phex protein is expressed in osteoblasts and osteocytes during the embryonic and postnatal periods and that within bone, Phex may be a unique marker for cells of the osteoblast/osteocyte lineage [27].
• In osteocytes, although the G6PD activity in each individual cell was unchanged by loading, the number of cells displaying activity was increased [28].

Analytical, diagnostic and therapeutic context of Osteocytes

• In situ hybridization studies were performed to examine the spatial and temporal expression patterns of Dmp1 during development in mouse embryos from 12.5 day postcoitus (dpc) to 8 weeks postnatal; these studies showed that Dmp1 first appeared in hypertrophic cartilage cells, followed by osteoblasts, and later was expressed strongly in osteocytes [29].
• Therefore, in this study, we have used a rat model of ovariectomy (OVX) to determine whether the effect of estrogen withdrawal extends to other species and to clarify the role of estrogen in the maintenance of osteocyte viability [30].
• In the current studies, expression of Bax, a proapoptotic gene product, and Bcl-2, an antiapoptotic gene product, was determined in osteocytes of fatigued rat bone using immunocytochemical staining and compared with TUNEL staining patterns [13].
• Mechanical reloading of the hind limbs after 14 days of tail suspension caused a transient increase within 2 h of the expression of cyclooxygenase (COX)-2 in intraosseous cells, composed mainly of osteocytes, and in the expression of c-fos in periosteal cells [31].
• A high dose of methylprednisolone was administered intramuscularly to rabbits, and we studied the accumulation of lipid in the osteocytes of the femoral head by histochemical methods and electron microscopy [32].

References