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At least 19 recordsLinked to original sources
PubMed2000

[Recent progress in studies on osteocytes--osteocytes and mechanical stress].

Although osteocytes are of the most abundant cells in bone, our knowledge about the role of osteocytes in bone metabolism is still poor compared with that about osteoblasts and osteoclasts, both being on the surface of bone. Osteocytes are terminally differentiated bone-forming cells. During bone formation, some of the osteoblasts lining the surface of bone are incorporated into the newly formed osteoid matrix and become osteocytes, while the other osteoblasts remain on the surface as lining cells. During this transition from osteoblasts to osteocytes, the cells lose numerous osteoblastic phenotypes and acquire osteocytic characteristics such as high expression of osteocalcin and particularly their specific morphology. Osteocytes are connected with each other in bone and with osteoblasts on the bone surface through canaliculi, forming cellular networks; and gap-junctions present at the contact sites mediate their intercellular communication. Several roles of osteocytes in bone have been proposed so far. Of them, based on the morphological characteristics of osteocytes, sensation of mechanical stress loaded onto bone is suspected to be one of their functions. One of the mechanical stresses on bone is fluid shear stress. Between the osteocyte's plasma membrane and the bone matrix is the periosteocytic space. This space exists both in the lacunae and in the canaliculi, and it is filled with extracellular fluid (ECF). Application of mechanical stress to bone locally deforms the tissue. This periodical deformation subsequently causes an increase in the flow of ECF in the periosteocytic space, resulting in shear stress on the surface of the osteocytes. Experimental studies demonstrated that bone cells were equivalently or more sensitive to the fluid shear stress than epithelial cells. Osteocytic cells cultured enhanced expression of prostaglandin (PG) G/H synthase-2 (COX-2) mRNA in response to shear stress. PGE2 is a potent regulator of proliferation and function of osteoblasts and osteoclasts. Therefore, a metabolic response by osteoblasts and osteoclasts lining the bone surface may be caused by PGE2 produced by osteocytes in response to shear stress when the prostanoid reaches the surface through the canaliculi. In conclusion, osteocytes play an important role in sensing extracellular mechanical stress, and the mechanical signals mediated by osteocytes may regulate the overall metabolism of cells in bone tissue.

Animals↗
PubMed1998

Osteocyte shape is dependent on actin filaments and osteocyte processes are unique actin-rich projections.

Osteocytes are derived from a select group of osteoblasts that have undergone a final differentiation. Due to their inaccessibility when embedded in the bone matrix, very little is known about the osteocyte cytoskeleton. This study provides an extensive analysis of the osteocyte cytoskeleton, based on the successful isolation of osteocytes from 16-day embryonic chick calvariae. We used OB7.3, a chicken osteocyte-specific monoclonal antibody, to confirm the osteocytic phenotype of the isolated cells and established culture conditions to promote growth of cells that most resemble osteocytes in vivo. Immunofluorescence staining with antitubulin, antivimentin, and antiactin showed the relative distribution of the microtubules, intermediate filaments, and actin filaments in both osteocyte cell body and processes. Field emission scanning electron microscopy revealed the three-dimensional relationships of the cytoskeletal elements and a unique organization of actin bundles that spanned the cell body and osteocyte processes. When combined with drug studies, these experiments demonstrate that actin filaments are crucial for the maintenance of osteocyte shape. Furthermore, we identified two actin-bundling proteins, alpha-actinin and fimbrin, in osteocyte processes. The prominence and unique distribution of fimbrin in osteocyte processes provides the possibility of its use as an intracellular marker to distinguish osteocytes from osteoblasts.

Actinin↗
PubMed2001

Osteocyte-osteoclast morphological relationships and the putative role of osteocytes in bone remodeling.

An osteocyte lacunae differential count under the light microscope (LM) (1-lacunae with live osteocytes, 2-empty lacunae and lacunae with degenerating osteocytes) was carried out outside the reversal lines of osteonic lamellar bone from various mammals and man to evaluate the possibility of osteocyte survival where osteoclast resorption had occurred. The polarized light microscope (PLM) was used to establish the curvature of bony lamellae outside the convexity of reversal lines: concave lamellae indicate osteocytes reabsorbed on their vascular side where they radiate long vascular dendrites; convex lamellae indicate bone resorption on the osteocyte mineral side, radiating short dendrites. In all samples it was found that: a) about 60% of osteocytes outside the reversal lines were live; b) the percentage of alive osteocytes close to reversal lines is higher when they are attacked on their mineral side. The present data support our view that surviving osteocytes, particularly those attacked from their mineral side, might intervene in the final phase of bone resorption (osteoclast inhibition?). The fact that under the transmission electron microscope (TEM) intercellular contacts were never observed between osteocytes and osteoclasts indicates that if a modulation should occur between these two cellular types it could take place by a paracrine route only. The putative role of the cells of the osteogenic system, particularly osteocytes, in the bone remodeling cycle is also discussed.

Journal Article↗
PubMed2003

The reaction of osteoclasts when releasing osteocytes from osteocytic lacunae in the bone during bone modeling.

Osteocytes are released from the osteocytic lacunae when osteoclasts resorb the bone matrix during bone modeling and remodeling. It remains unknown how osteoclasts react when releasing osteocytes during bone modeling, and the fate of these released osteocytes is also unclear. Femoral mid-shafts of 2-day-old kittens were sectioned into serial 0.5 microm-thick semithin or 0.1 microm-thick ultrathin sections, and examined by light microscopy (LM) and transmission electron microscopy (TEM). The sections showed many osteoclasts at the endosteum but there were no osteoblasts. There were many half-released, fully released, half-exposed, and fully exposed osteocytes on the bone surfaces. Many cell-like structures were seen in the cell bodies of osteoclasts by LM, and some semithin sections were re-sectioned into ultrathin sections for re-observation by TEM. By TEM, these were determinated to be mononuclear cells. The serial ultrathin sections showed that the mononuclear cells appeared to be engulfed in osteoclasts on one section but that the cell was connected with the bone surface of the osteocytic lacuna on another section. These results show that the mononuclear cells in the osteoclasts were osteocytes. The present study suggests that osteoclasts engulf some osteocytes but do not engulf others when releasing osteocytes during bone modeling.

Animals↗
PubMed2004

Matrix metalloproteinases (MMPs) safeguard osteoblasts from apoptosis during transdifferentiation into osteocytes: MT1-MMP maintains osteocyte viability.

Osteoblasts undergo apoptosis or differentiate into either osteocytes or bone-lining cells after termination of bone matrix synthesis. In this study, we investigated the role of matrix metalloproteinases (MMPs) in differentiation of osteoblasts, bone formation, transdifferentiation into osteocytes, and osteocyte apoptosis. This was accomplished by using calvarial sections from the MT1-MMP-deficient mouse and by culture of the mouse osteoblast cell line MC3T3-E1 and primary mouse calvarial osteoblasts. We found that a synthetic matrix metalloprotease inhibitor, GM6001, strongly inhibited bone formation in vitro of both primary osteoblasts and MC3T3 cells by approximately 75%. To further investigate at which level of osteoblast differentiation MMP inhibition was attenuating osteoblast function, we found that neither preosteoblast nor mature osteoblast activity was affected. In contrast, cell survival of osteoblasts forced to transdifferentiate into osteocytes in 3D type I collagen gels were inhibited by more than 50% when exposed to 10 microM GM6001 and to Tissue Inhibitor of Metalloproteinase-2 (TIMP-2), a natural MT1-MMP inhibitor. This shows the importance of MMPs in safeguarding osteoblasts from apoptosis when transdifferentiating into osteocytes. By examination of osteoblasts and osteocytes embedded in calvarial bone in the MT1-MMP deficient mice, we found that MT1-MMP deficient mice had 10-fold higher levels of apoptotic osteocytes than wild-type controls. We have previously shown that MT1-MMP activates latent Transforming Growth Factorbeta (TGF-beta). These findings strongly suggest that MT1-MMP-activated TGF-beta maintains osteoblast survival during transdifferentiation into osteocytes, and maintains mature osteocyte viability. Thus, the interrelationship of MMPs and TGF-beta may play an important role in bone formation and maintenance.

Animals↗
PubMed1976

The influence of immobilization on osteocyte morphology: osteocyte differential count and electron microscopical studies.

Differential counts and electron microscopical studies of osteocytes were performed on rats immobilized by spinal cord severing, plaster cast and ischiatic nerve dissection. In undecalcified ground sections of tibia and femur (100 micron) stained with basic fuchsin, osteocytes were differentiated into small (metabolically inactive) osteocy es enlarged (metabolically activated) osteocytes and empty lacunae. In rats (immobilizedfor' three weeks) with functioning parathyroid glands, but not after parathyroidectomy, the number of activated cells is markedly increased, whereas the number of small osteocytes is reduced. In animals with spinal cord severing the number of empty lacunae is also increased. Electron microscopical studies of undecalcified tibiae taken from rats immobilized for ten days showed a periosteocytic osteolysis with destruction of the lacunar wall, fragmentation of collagen fibres and loss of mineral crystals. The cytoplasmic seams of osteocytes were broadened, mitochondria were enlarged, and the cytoplasma showed vacuoles containing amorphous material which could be found in the pericellular space. Deep invaginations of the cytoplasma and an increase of the cell processes were typical findings. The results of the investigation point to an activation of osteocyte metabolism by immobilization. The osteocytes thus play an important part at the onset of immobilization osteoporosis. Periosteocytic osteolysis can be inhibited by parathyroidectomy. Therefore, the response of osteocytes to endogenous parathyroid hormone must be altered under conditions of immobilization.

Animals↗
PubMed1986

Identification of osteocytes in osteoblast-like cell cultures using a monoclonal antibody specifically directed against osteocytes.

The development of a monoclonal antibody, OB 7.3, directed against a cell surface antigenic site on osteocytes is described. Osteoblast-like cells were enzymatically isolated from calvaria of chicken embryos after removal of the periostea. The cells were cultured for 6 days, harvested and used to immunize mice. One of the monoclonal antibodies obtained, OB 7.3, reacted specifically with the cell surface of osteocytes. In frozen sections of bone only osteocytes were stained, all other cells present, including mature osteoblasts, were negative. Liver, kidney, spleen, intestine, bloodvessel and skin were also completely negative. Using the monoclonal OB 7.3, positive cells could be demonstrated in sparse osteoblast-like cell cultures. The OB 7.3 positive cells had a stellate morphology and were therefore identified as osteocytes. They behaved in culture as osteocytes in bone tissue in that they formed a network of cell processes connecting osteocytes with each other or with other neighbouring cells. Monoclonal OB 7.3 offers the possibility of isolating osteocytes thereby providing the means for a detailed study of their biochemical properties.

Animals↗
PubMed1979

An electron microscopic investigation of human familial bone dysplasia. Inhibition of osteocytic osteolysis and induction of osteocytic formation of elastic fibers following calcitonin treatment.

Familial bone dysplasia with hyperphosphatasemia is characterized by excessive bone resorption early in life with resulting severe skeletal deformity. The disease can be ameliorated by treatment with human calcitonin. We have the studied the ultrastructure of bone from diseased patients before treatment and at intervals during 1 year of treatment with calcitonin. Pretreatment osteoblasts, osteoclasts, and osteocytes exhibited mitochondria which contained vast amounts of dense microcrystal deposits. Osteocytes were also distinguished by minimal organellar development. Osteoclasts were rare. Calcitonin treatment included a progressive development of a more normal bone structure. Intramitochondrial crystal deposits were absent in mitochondria of osteocytes and osteoclasts but were still present in mitochondria of osteoblasts. Surprisingly, the developing bony matrix during calcitonin treatment exhibited large numbers of elastic fibers. These appeared to develop normally in alignment with the surface membrane of osteocytes. Calcitonin treatment caused a proliferation of osteocyte organellar development. It is concluded that familial bone dysplasia is primarily a disease of osteocytes and that osteocytic activity is influenced by calcitonin.

Bone Diseases, Developmental↗
PubMed2000

Osteocyte function, osteocyte death and bone fracture resistance.

The function of the most numerous cell in bone, the osteocyte, has until recently been mysterious and at times controversial. There is now an emerging consensus that osteocytes modulate signals arising from mechanical loading and so direct the appearance and disappearance of bone tissue at the microscopic level, which allows bone as an organ both to grow and to adapt efficiently to the body's mechanical needs for strength with lightness. Osteocytes appear to use some molecular signalling pathways that are familiar from other tissues, such as the generation of nitric oxide and prostaglandins as well as directing cell-cell communication via gap junctions. They may also direct the removal of damaged or redundant bone through mechanisms linked to their own apoptosis or via the secretion of specialised cellular attachment proteins such as osteopontin. Osteocytes possess receptors for parathyroid hormone/parathyroid hormone related peptide and both oestrogen receptors alpha and beta. They also express molecules which in nerve cells are involved with glutamate neuro-transmission. At least some of these receptors and their ligands may regulate osteocyte apoptosis and modulate osteocyte signalling.

Animals↗
PubMed2003

CD40 ligand blocks apoptosis induced by tumor necrosis factor alpha, glucocorticoids, and etoposide in osteoblasts and the osteocyte-like cell line murine long bone osteocyte-Y4.

During characterization of the osteocyte-like murine long bone osteocyte-Y4 (MLO-Y4) cell line, comparison was made with antigen-presenting cells of the immune system known as dendritic cells. It was observed that the MLO-Y4 osteocyte-like cells express CD40 antigen and MHC class I antigen, but they are negative for a series of other dendritic cells markers (DEC-205, CD11b, CD11c, CD86, and MHC class II) and immune cell markers [CD45, CD3, CD4, B220, Gr-1, and CD40 ligand (CD40L)]. RT-PCR results showed expression of CD40 mRNA and lack of CD40L mRNA expression. Like MLO-Y4 osteocyte cells, both primary osteoblasts and the osteoblast-like cell lines MC3T3, OCT-1, and 2T3 were shown to express CD40 antigen by fluorescence-activated cell sorting. Because CD40L has been shown to function as an antiapoptotic factor in dendritic cells, it was reasoned that this molecule may have a similar function in bone cells. In three different assays for apoptosis, including trypan blue exclusion, changes in nuclear morphology, and fluorescence-activated cell sorting staining for annexin V/propidium iodide, CD40L significantly inhibited apoptosis of MLO-Y4 cells induced by dexamethasone, TNF alpha, or etoposide. CD40L also inhibited dexamethasone and TNF alpha-induced apoptosis in the osteoblast cell lines, OCT1 and MC3T3-E1. These data support the hypothesis that CD40L preserves viability of osteoblasts and osteocytes against a wide variety of apoptotic factors independent of signaling or transcriptional mechanisms. Because osteocyte cell death appears to result in bone loss, these studies have important implications for the treatment of bone loss due to glucocorticoid excess and/or to osteoporosis in general.

Animals↗
PubMed1984

Metabolic pathways of the fossil dinosaur bones. Part IV. Modes of linkage between osteocytes and a variety of nexuses of osteocytes processes.

Examinations were carried out on the fossil dinosaur bones 80 million years old. Samples for examination were prepared with specially elaborated methods. The light, transmission electron, and sanning electron microscopic images showed the spatial distribution of osteocytes with the system of processes as well as by thin and short ones. The axial processes, retaining the same diameter along their entire course, usually connected the polar parts of the osteocytes which frequently lay considerable distance apart. Such connections were of two kinds. In one case the link was attained by catoplasmic continuity. In the other, the processes belonging to one osteocyte came into contact with definite spot of plasmalemma of another osteocyte by means of a terminal, club-shaped widening, the so called contact body. This spot looked like a hollow or a conical protuberance. In this type of contact there were always tiny apertures between the contacting elements. Moreover, three types of contact, especially between thin processes, were distinguished, i.e. "end to end", "side to side", and "end to side". It seems that direct connections achieved through cytoplasmic continuity are utilized in rapid exchange, which may be indicated by the thickness of processes and the lack of a membranous barrier. The remaining, indirect links (with participation of membranes) though varied in the type of contact seem to fulfil identical functions.

Animals↗
PubMed1989

An electron microscopic study of the changes observed in osteocytes under ischemic conditions.

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. Five female Japanese white rabbits were used in this study. Osteochondral chips were taken from one side of the femoral condyle, covered with Millipore filters, and then inserted into the other side of the knee joint. These tissues were examined after 12 h and after 2, 5, 8, and 14 days of ischemia under both light and electron microscopy. Under light microscopy, osteocytes and lacunae were classified into four types: normal osteocyte, pyknotic osteocyte, pale osteocyte, and empty osteocyte lacuna. The number of each type of osteocyte (or lacuna) in a settled area was counted. The ratio of normal osteocytes decreased significantly (p less than 0.001) after the second day of ischemia. Pyknotic osteocytes increased at 12 h (p less than 0.01) and 2 days (p less than 0.001) of ischemia. On the fifth day of ischemia, the percentage of pale osteocytes reached a peak. This was followed by a gradual increase in the number of empty lacunae. On the fourteenth day of ischemia, empty lacunae constituted greater than 40% of the cell types. When viewed by electron microscopy, these necrotic osteocytes were similar to the degenerative osteocytes that have been observed in physiological states and apparently different from lipid-accumulating osteocytes. The results suggested that there could be at least two types of necrotic processes in osteocytes that eventually lead to cell death.

Animals↗
PubMed2002

The role of osteocytes in bone regulation: mineral homeostasis versus mechanoreception.

Early work on the role of osteocytes in bone regulation suggested that the primary function of these cells was osteolysis. This lytic function was not precisely defined but included mineral homeostasis and at least the initiation of matrix remodeling, if not a primary role in remodeling. This paper is an attempt to promote the concept of osteocytic osteolysis as a method of systemic mineral homeostasis and to separate it from bone remodeling. Although recent investigations have pointed to mechanotransduction as a primary function of osteocytes, resulting in a general abandonment of the osteocytic osteolysis concept, the corpus of evidence suggests that osteocytes likely have a multipurpose role in the biology of bone. The osteocyte network represents an enormous surface area over which the cells interface with the surrounding matrix, useful for both strain detection and matrix mineral access. Osteocytes have been found to possess receptors for PTH, a known regulator of mineral ion homeostasis. Cultured osteocytes placed on dentin slices demonstrated no capacity to pit the dentin, but they were not treated with a regulating factor such as PTH, nor does mineral homeostasis require substantial bone volume removal. Scaling relationships suggest that osteocyte density is inversely proportional to body mass, R(2) = 0.86, and thus directly proportional to metabolic rate. Thus, species with higher metabolic rates (and therefore a greater demand for immediate access to minerals) have more osteocytes per bone volume. Finally, osteocytes express molecules typically associated with nerve cells and which are involved with glutamate neurotransmission. By this system, almost instantaneous messages may be transmitted throughout the network, an important feature in cells whose homeostatic function would be utilized on a scale of seconds, rather than hours or days. Experimental procedures for determining the role of the osteocyte in mineral homeostasis would require calcium mobilization from the bone matrix on a relatively immediate time scale. The experimental procedure would then be coupled with a high resolution histomorphometric analysis of lacunar radiographic area and mineral density. Added to this would be an in vitro study of mineral activation capacity via cultured osteocytes treated with PTH. Osteocytic osteolysis would be confirmed by an increase in the demineralized volume of osteocytic lacunae and the identification of a chemical mechanism by which osteocytes can readily access the mineral portion of their immediate bone matrix. It should also be true that a reverse capacity exists by which osteocytes can remineralize their immediate matrix utilizing alkaline phosphatase for example, a chemical which they, like osteoblasts, are known to generate. It is thus proposed that osteocytes are both mechanoreceptors and systemic mineral homeostasis regulators.

Journal Article↗
PubMed2000

Some osteocytes released from their lacunae are embedded again in the bone and not engulfed by osteoclasts during bone remodeling.

It is generally accepted that osteocytes derive from osteoblasts that have secreted the bone around themselves. Osteocytes are cells embedded in the lacunae in the bone, and they are characteristically in contact with other cells by many slender cytoplasmic processes in canaliculi. During bone remodeling, many osteocytes in the bone are released from their lacunae by osteoclasts; however it remains unclear what happens to these released osteocytes. The cortical bone of the rat mandibular body was used in this study. Mandibles were fixed, decalcified, and then embedded in Epon 812. Specimens were sectioned in the frontal direction into serial 0.5 microm-thick semithin or 0.1 microm-thick ultrathin sections, and then examined by light or transmission electron microscopy. Cells that fitted in the osteocytic lacunae with canaliculi extending to the bone were identified as osteocytes in this study. Among many osteocytes released by osteoclasts in cutting cones, there were osteocytes half-released from their lacunae. These cells fitted in their lacunae with canaliculi extending to the bone and showed developed cell organelles in the cytoplasm. In closing cones, many osteocytes were situated in the bone away from cement lines; however, there were half-embedded osteocytes in the bone formed on cement lines. These cells fitted in their lacunae with canaliculi extending to the bone formed below cement lines and showed developed cell organelles in the cytoplasm. These results show that half-embedded osteocytes in closing cones derive from half-released osteocytes in cutting cones. Osteocytes encircled by osteoclasts were sometimes observed on one section, but serial sections showed that these osteocytes fitted in their remaining lacunae in the bone on other sections. This shows that not all osteocytes released from their lacunae are engulfed by osteoclasts. Consequently, the present results suggests that some osteocytes released from their lacunae are embedded again in the bone and not engulfed by osteoclasts during bone remodeling.

Animals↗