Within the past few years, information regarding osteocyte function as been emerging and expanding significantly. No longer is the osteocyte considered a passive cell acting simply as a 'placeholder' within mineralized bone. Osteocytes are derived from osteoblast progenitors and in the adult skeleton compose 90-95% of all bone cells. Therefore, the function of these cells in the adult and aging skeleton has become the focus of recent investigation. These cells are proving to be multifunctional, ranging from mechanotransduction, to regulation of mineral homeostasis, to control of bone remodeling. The osteocyte as a source and reservoir of signaling factors important in health and maintenance of the adult skeleton is addressed in this review.
Adult ; Aging ; Bone Remodeling ; Homeostasis ; Humans ; Osteoblasts ; Osteocytes ; Skeleton

PURPOSE: The present study was performed to determine the optimum conditions(RPM, load, sharpness of drill) for drilling human cortical bone with standard drill, and to evaluate the histological changes occuring in bone after drilling. MATERIALS AND METHODS: in experiment I, we measured temperature elevations and the durations of temperature elevation in cadaveric femoral cortices at specific distances from the drill hole wall while drilling. The effects of drilling force, speed and new versus worn drill on the termperature were determined. In experiment II, we also measured temperature elevations in the same manner in porcine femoral cortices and evaluated the histological changes occuring in bone after drilling. RESULTS: In experiment I, the most significant temperature elevation(68.4degrees C ) was found when worn drill was used. The lower drilling force and faster speed resulted in 55.1degrees C and 45.8degrees C temperature elevation, respectively. However, drill diameter was not a significant factor for temperature elevation. In experiment II, greater heat production was measured with worn drill, at lower drilling forces, at faster drill speed. The acute histologic reactions in bone were hyperemia, degeneration of osteocytes, change in bone stainability, tears, and fragmentation of the bone edges around the drill holes. The observed histological changes were proportional to the amount of trauma produced, that is, the greater the degree of thermal irritation, the greater the degree of histologic activity. CONCLUSION: In cortical drilling, greater heat production was measured with worn drill, at lower drilling forces, at faster drill speed and the greater the degree of thermal irritation, the greater the degree of histologic activity. A further study of the reaction of bone to drilling at longer intervals of time at different conditions may possibly show whether aseptic thermal necrosis could be prevented.
Cadaver ; Hot Temperature* ; Humans ; Hyperemia ; Necrosis* ; Osteocytes ; Thermogenesis*

The last decade has seen an exponential increase in our understanding of osteocytes function and biology. These cells, once considered inert by-standers trapped into the mineralized bone, has now risen to be key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. As tools and techniques to study osteocytes improved and expanded, it has become evident that there is more to these cells than initially thought. Osteocytes are now recognized not only as the key responders to mechanical forces but also as orchestrators of bone remodeling and mineral homeostasis. These cells are the primary source of several important proteins, such as sclerostin and fibroblast growth factor 23, that are currently target as novel therapies for bone loss (as the case for antisclerostin antibodies) or phosphate disorders. Better understanding of the intricate cellular and molecular mechanisms that govern osteocyte biology will open new avenue of research and ultimately indentify novel therapeutics to treat bone and mineral disorders. This review summarizes novel findings and discusses future avenues of research.
Biology ; Bone Remodeling ; Fibroblast Growth Factors ; Hematopoiesis ; Homeostasis ; Metabolism ; Osteocytes*

The last decade has seen an exponential increase in our understanding of osteocytes function and biology. These cells, once considered inert by-standers trapped into the mineralized bone, has now risen to be key regulators of skeletal metabolism, mineral homeostasis, and hematopoiesis. As tools and techniques to study osteocytes improved and expanded, it has become evident that there is more to these cells than initially thought. Osteocytes are now recognized not only as the key responders to mechanical forces but also as orchestrators of bone remodeling and mineral homeostasis. These cells are the primary source of several important proteins, such as sclerostin and fibroblast growth factor 23, that are currently target as novel therapies for bone loss (as the case for antisclerostin antibodies) or phosphate disorders. Better understanding of the intricate cellular and molecular mechanisms that govern osteocyte biology will open new avenue of research and ultimately indentify novel therapeutics to treat bone and mineral disorders. This review summarizes novel findings and discusses future avenues of research.
Biology ; Bone Remodeling ; Fibroblast Growth Factors ; Hematopoiesis ; Homeostasis ; Metabolism ; Osteocytes*

Osseous choristoma rarely occurs, but when it does, the oral cavity of the head and neck lesion is the most common site. It appears as a mass of normal bony structure, consisting of mature osteocytes in an ectopic position. Appearing as a calcification of thyroid mass on radiologic examinations, it could be a benign lesion, chronic inflammation, or carcinoma; the final diagnosis can only be obtained by a pathologic confirmation. Histologically, the lesions show a well-circumscribed mass of vital bone. The treatment of choice is surgical excision. We report a case of osseous choristoma that occurred on the thyroid gland. To our knowledge, such has not been reported previously as a site of osseous choristoma.
Choristoma ; Head ; Inflammation ; Mouth ; Neck ; Osteocytes ; Thyroid Gland

The aim of this study was to investigate the role of osteal macrophages (osteomac) and osteocytes in bone remodeling using a mathematical model. We constructed the bone system with pre-osteoblasts, osteoclasts, osteocytes, and osteomac. Each link of the parameters and ordinary differential equations followed the Graham's model in 2013 except for the parameters of osteomac signaling and osteocytes signaling to link preosteoblasts and osteoblasts. We simulated the changes in each cell and bone volume according to the changes in the parameters of osteomac signaling and osteocytes signaling. The results showed bone volume was unstable and decreased gradually when the effectiveness of osteocytes and osteomac dropped below a certain level. When the parameters of osteomac signaling and osteocytes signaling to link preosteoblasts and osteoblasts had a value less than 1, bone volume increased with the increase in the parameter of osteomac signaling to link preosteoblasts and osteoblasts. Moreover, although the parameter of osteocytes signaling to link preosteoblasts and osteoblasts, increased in case of a small parameter of osteomac signaling, bone volulme decreased. If the parameters of osteomac signaling to link preosteoblasts and osteoblasts were over a certain level, bone volume was positively maintained, despite the parameter of osteocyte signaling to link preosteoblasts and osteoblasts. We suggested the osteomac may affect bone remodeling and may play an important role in bone cell network.
Bone and Bones* ; Bone Remodeling ; Macrophages* ; Models, Theoretical* ; Osteoblasts ; Osteoclasts ; Osteocytes*

OBJECTIVE: To assess the value of Ploton silver staining and phalloidin-iFlour 488 staining in observation of the morphology of osteocyte dendrites of mice at different developmental stages. METHODS: The humerus and femurs were harvested from mice at 0 (P0), 5 (P5), 15 (P15), 21 (P21), 28 (P28), and 35 days (P35) after birth to prepare cryo-sections and paraffin sections. HE staining of P35 mouse femur sections served as a reference for observing osteocytes in the trabecular bone and cortical bone. The humeral sections at different developmental stages were stained with Ploton silver staining to observe the morphology of osteocytes and canaliculi, and the canalicular lengths in the cortical and trabecular bones of the humerus of the mice in each developmental stage were recorded. The cryo-sections of the humerus from P10 and P15 mice were stained with phalloidin iFlour-488 to observe the morphology of osteocytes and measurement of the length of osteocyte dendrites in the cortical bone. RESULTS: In the trabecular bone of the humerus of P0-P15 mice, Ploton silver staining only visualized the outline of the osteocytes, and the morphology of the canaliculi was poorly defined. In P21 or older mice, Ploton silver staining revealed the morphology of the trabecular bone osteocytes and the canaliculi, which were neatly arranged and whose lengths increased significantly with age (P21 CONCLUSIONS Mouse osteocyte dendrites elongate progressively and their arrangement gradually becomes regular with age. Ploton silver staining can clearly visualize the morphology of the osteocytes and the canaliculi in adult mice but not in mice in early stages of development. Phalloidin iFlour-488 staining for labeling the cytoskeleton can be applied for mouse osteocytes at all developmental stages and allows morphological observation of mouse osteocytes in early developmental stages.
Animals ; Bone and Bones ; Dendrites ; Mice ; Osteocytes ; Phalloidine ; Silver Staining

OBJECTIVE: To investigate the mechanism of the participation of osteocytes in the formation of osteoclasts under hypoxia. METHODS: The hypoxia culture system of osteocyte-like cell line MLO-Y4 was established by deferoxamine mesylate (DFO) in vitro. The proliferation of MLO-Y4 cells was examined by CCK-8 cell proliferation/toxicity assay. RAW264.7 cells were induced to osteoclasts by the conditioned medium containing the cultured MLO-Y4. Tartrate-resistant acid phosphatase (TRAP) staining was performed on day 7. Quantitative real-time fluorescence polymerase chain reaction, immunofluorescence, and Western blot were used to detect the expression levels of hypoxia-inducible factor (HIF)-1α and receptor activator of nuclear factor-κB ligand (RANKL) in MLO-Y4 under hypoxia. The effects of siHIF-1α on the expression levels of HIF-1α and RANKL in MLO-Y4 under the same conditions were detected. RESULTS: DFO (100 μmol·L⁻¹) promoted the proliferation of MLO-Y4 at 24 h, which decreased with time (P<0.01). After the addition of soluble sRANKL, the formation of osteoclasts was significantly increased in the DFO group (P<0.001). The expression of RANKL mRNA in MLO-Y4 under 100 μmol·L⁻¹ DFO increased first and then decreased with the duration of hypoxia. This expression reached a peak at 24 h (P<0.01). Hypoxia up-regulated the expression of HIF-1α and RANKL protein (P<0.01). Under hypoxia, siHIF-1α downregulated the expression of HIF-1α and RANKL (P<0.01). siHIF-1α also decreased the number of osteoclasts (P<0.01). CONCLUSIONS Under hypoxia, MLO-Y4 could facilitate the formation of RANKL through upre-gulating the expression of HIF-1α protein, thereby accelerate the differentiation of RAW264.7 cells into osteoclasts.
Cell Differentiation ; Cell Line ; Humans ; Hypoxia ; Osteoclasts ; Osteocytes

Bone is continuously remodelled at many sites asynchronously throughout the skeleton, with bone formation and resorption balanced at these sites to retain bone structure. Negative balance resulting in bone loss and osteoporosis, with consequent fractures, has mainly been prevented or treated by anti-resorptive drugs that inhibit osteoclast formation and/or activity, with new prospects now of anabolic treatments that restore bone that has been lost. The anabolic effectiveness of parathyroid hormone has been established, and an exciting new prospect is presented of neutralising antibody against the osteocyte protein, sclerostin. The cellular actions of these two anabolic treatments differ, and the mechanisms will need to be kept in mind in devising their best use. On present evidence it seems likely that treatment with either of these anabolic agents will need to be followed by anti-resorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for safe, effective anti-resorptive drugs.
Anabolic Agents ; Bone and Bones ; Bone Density Conservation Agents ; Osteoclasts ; Osteocytes ; Osteogenesis ; Osteoporosis ; Parathyroid Hormone ; Skeleton

Cultures of primary human alveolar bone-derived cells were established from alveolar bone chips obtained from normal individuals undergoing tooth extraction. These cells were expanded in vitro until passage 3 and used for the in vivo assays. Cells were loaded into transplantation vehicles, and transplanted subcutaneously into immunodeficient mice to study the capacities of human alveolar bone-derived cells to form bone in vivo. Transplants were harvested 12 weeks after transplantation and evaluated histologically. Of 10 human alveolar bone-derived cell transplants, two formed a bone-like tissue that featured osteocytes and mineral. Eight of the ten formed no osseous tissue. These results show that cells from normal human alveolar bone are capable of forming bone-like tissue when transplanted into immunodeficient mice.
Animals ; Cell Culture Techniques ; Humans* ; Mice ; Osteocytes ; Osteogenesis* ; Tissue Engineering ; Tooth Extraction ; Transplants