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At least 397 records · Page 22Linked to original sources
PubMed1994

Calmodulin concentrated at the osteoclast ruffled border modulates acid secretion.

Osteoclasts mediate acid dissolution of bone for maintenance of serum [Ca2+] and for replacement of old bone in terrestrial vertebrates. Recent findings point to the importance of intracellular signals, particularly Ca2+, in osteoclast regulation. However, acid degradation of bone mineral subjects the osteoclast to uniquely high extracellular [Ca2+]. We hypothesized that this high calcium environment would affect calcium signalling mechanisms, and studied the calcium binding regulatory protein, calmodulin, in the osteoclast. Avian osteoclast bone resorption was inhibited 30% at 1 microM and 90% at 7 microM by the calmodulin antagonist trifluoperazine. Osteoclast bone attachment was not affected by 10 microM trifluoperazine. Quantitative immunofluorescence using fluorescein-labelled calmodulin monoclonal antibody showed a severalfold increase of calmodulin concentration in bone attached relative to plastic attached osteoclasts. Western blots confirmed this, showing two to threefold increased osteoclast calmodulin per milligram of cell protein in 3-day bone-attached vs. nonattached cells. Scanning confocal microscopy showed calmodulin polarization to areas of bone attachment. Electron micrographs with 9 nm colloidal gold labelling showed calmodulin in the acid secreting ruffled membrane. ATP-dependent acid transport in osteoclast membrane vesicles was inhibited by the calmodulin antagonist calmidazolium. This effect was reversed by addition of excess calmodulin, showing that the inhibition is specific. Vesicle acid transport inhibition reflects an approximately fourfold shift in the apparent Km for ATP of vesicular acid transport in the presence of the calmodulin antagonist. We conclude that calmodulin concentration and distribution is modified by bone attachment, and that osteoclastic acid secretion is calmodulin regulated.

Acids↗
PubMed2003

Osteoclast diseases.

Osteoclasts are the only cells capable of resorbing mineralised bone, dentine and cartilage. Osteoclasts act in close concert with bone forming osteoblasts to model the skeleton during embryogenesis and to remodel it during later life. A number of inherited human conditions are known that are primarily caused by a defect in osteoclasts. Most of these are rare monogenic disorders, but others, such as the more common Paget's disease, are complex diseases, where genetic and environmental factors combine to result in the abnormal osteoclast phenotype. Where the genetic defect gives rise to ineffective osteoclasts, such as in osteopetrosis and pycnodysostosis, the result is the presence of too much bone. However, the phenotype in many osteoclast diseases is a combination of osteosclerosis with osteolytic lesions. In such conditions, the primary defect is hyperactivity of osteoclasts, compensated by a secondary increase in osteoblast activity. Rapid progress has been made in recent years in the identification of the causative genes and in the understanding of the biological role of the proteins encoded. This review discusses the known osteoclast diseases with particular emphasis on the genetic causes and the resulting osteoclast phenotype. These human diseases highlight the critical importance of specific proteins or signalling pathways in osteoclasts.

Animals↗
PubMed1982

Calcitonin alters behaviour of isolated osteoclasts.

Osteoclasts were incubated on a glass or plastic substrate and the effect of calcitonin (CT) on their behaviour was observed. Before exposure to CT the osteoclasts were actively motile, the cytoplasm advancing behind broad pseudopodial (lamellipodial) processes which showed intense ruffling activity. CT caused cessation of lamellipodial activity within minutes, followed by gradual fragmentation and retraction of lamellipodia. Complete osteoclast quiescence was regularly induced by concentrations of CT above 50 pg/ml, and lesser degrees of quiescence were induced at concentrations down to 10 pg/ml. This quiescent state was reversed on removing CT from the medium, and was abrogated by prior treatment of osteoclasts with trypsin. The quiescent state did not reduce the longevity of the cells in culture, nor did it affect their resistance to removal from glass by trypsin. CT showed no influence on the pseudopodial activity of osteoclasts, peritoneal macrophages or inflammatory giant cells. Osteoclast quiescence seems to be a reversible state induced by the interaction of CT with a trypsin-sensitive CT receptor, present on osteoclasts. The range of concentrations which induce partial osteoclast quiescence are within the physiological range of serum concentrations in man, and this suggests that CT plays a physiological role in the regulation of osteoclasts may help to identify the precursor cell of the osteoclast and may assist investigations into the mechanism of control of osteoclasis.

Animals↗
PubMed2007

Osteoclast nuclei of myeloma patients show chromosome translocations specific for the myeloma cell clone: a new type of cancer-host partnership?

A major clinical manifestation of bone cancers is bone destruction. It is widely accepted that this destruction is not caused by the malignant cells themselves, but by osteoclasts, multinucleated cells of monocytic origin that are considered to be the only cells able to degrade bone. The present study demonstrates that bone-resorbing osteoclasts from myeloma patients contain nuclei with translocated chromosomes of myeloma B-cell clone origin, in addition to nuclei without these translocations, by using combined FISH and immunohistochemistry on bone sections. These nuclei of malignant origin are transcriptionally active and appear fully integrated amongst the other nuclei. The contribution of malignant nuclei to the osteoclast population analysed in this study was greater than 30%. Osteoclast-myeloma clone hybrids contained more nuclei than normal osteoclasts and their occurrence correlated with the proximity of myeloma cells. Similar hybrid cells were generated in myeloma cell-osteoclast co-cultures, as revealed by tracing myeloma nuclei using translocations, bromo-deoxyuridine, or the Y chromosome of male myeloma cells in female osteoclasts. These observations indicate that hybrid cells can originate through fusion between myeloma cells and osteoclasts. In conclusion, malignant cells contribute significantly to the formation of bone-resorbing osteoclasts in multiple myeloma. Osteoclast-myeloma clone hybrids reflect a previously unrecognized mechanism of bone destruction in which malignant cells participate directly. The possibility that malignant cells corrupt host cells by the transfer of malignant DNA may have been underestimated to date in cancer research.

Acid Phosphatase↗
PubMed2001

Cellular and humoral mechanisms of osteoclast formation and bone resorption in Gorham-Stout disease.

Gorham-Stout disease (GSD) is a rare, massively osteolytic condition which is associated with increased vascularity and an increase in osteoclast numbers. To determine the cellular and humoral mechanisms underlying the increase in osteoclast numbers and osteolysis in GSD, this study analysed circulating osteoclast precursor numbers and sensitivity to osteoclastogenic factors in a GSD patient and age/sex-matched controls. Monocytes were cultured with M-CSF (25 ng/ml) and RANKL (30 ng/ml) and osteoclast formation was assessed in terms of the formation of TRAP(+) and VNR(+) multinucleated cells and the extent of lacunar resorption. There was no increase in the proportion of circulating osteoclast precursors in GSD relative to controls, but lacunar resorption was consistently greater in GSD monocyte cultures. Increased osteoclast formation in GSD was noted when monocytes were incubated with IL-1beta (1 ng/ml), IL-6/sIL-6R (100 ng/ml), and TNFalpha (10 ng/ml). An increase in osteoclast differentiation and bone resorption was also noted in control monocyte cultures in the presence of GSD serum. These results indicate that the increase in osteoclast formation in GSD is due not to an increase in the number of circulating osteoclast precursors, but rather to an increase in the sensitivity of these precursors to humoral factors which promote osteoclast formation and bone resorption.

Carrier Proteins↗
PubMed1998

Tyro 3 receptor tyrosine kinase and its ligand, Gas6, stimulate the function of osteoclasts.

Bone is continuously being formed and resorbed. This process is accomplished by the precise coordination of two cell types: osteoblasts and osteoclasts. Osteoclasts are large, multinucleated cells that are derived from the same hematopoietic precursors as macrophages. However, these bone-resorbing cells are difficult to study directly because of their relative inaccessibility. The purification of primary osteoclasts from rabbit bones by their adherent nature provides an opportunity for investigating the molecules in osteoclasts. We have examined the expression of receptor tyrosine kinase by polymerase chain reaction (PCR) and found that Tyro 3 was frequently identified from primary osteoclasts in PCR cloning. Immunohistochemistry revealed that Tyro 3 was expressed on the multinucleated osteoclasts which were positive for tartrate-resistant acid phosphatase (TRAP), but not on mononuclear TRAP-positive cells. The Tyro 3 ligand, Gas6, induced the phosphorylation of Tyro 3 receptors in osteoclasts in two to five min. Gas6 and protein S directly enhanced the bone resorbing activity of mature osteoclasts. This effect of Gas6 was inhibited by the addition of a tyrosine kinase inhibitor, herbimycin A. However, Gas6 did not affect the differentiation of osteoclasts from bone marrow cells. Gas6 and protein S are dependent on vitamin K, a cofactor for the enzyme responsible for carboxylation of glutamic acid residues. The findings in this study are the first to indicate a new biological activity of Gas6 and protein S as a direct regulator of osteoclastic function; they give an insight into the role of these vitamin K-dependent ligands in bone resorption in vivo.

Acid Phosphatase↗
PubMed1994

A reappraisal of the effect of extracellular calcium on osteoclastic bone resorption.

During bone resorption osteoclasts are exposed to high levels of extracellular calcium solubilized from bone mineral and it has been suggested that this may act as a physiological negative feedback to control the resorptive process. We have confirmed that calcium (1.5-20 mM) dose-dependently inhibits osteoclastic bone resorption when added at the start (t = 0 hr) of the 24 hr bone slice assay. When 20 mM calcium was added at t = 0, 1, 3 or 6 hr after osteoclast attachment to bone slices, resorption was inhibited by 100%, 100%, -10% and 6% respectively. In contrast, human calcitonin (1 ng/ml) inhibited bone resorption by 100%, 100%, 91% and 52% when added at t = 0, 1, 3 and 6 hr respectively. Osteoclasts were not seen on bone slices after 24 hr incubation when 20 mM calcium was added at t = 0 or 1 hr, but when calcium was added at t = 3 or 6 hr osteoclast numbers were similar to controls, indicating that 20 mM calcium is not toxic to osteoclasts. Human calcitonin did not significantly affect osteoclast numbers regardless of time of addition to the bone slice assay. The absence of osteoclasts on bone slices exposed to 20 mM calcium at early time points indicates that high levels of extracellular calcium prevent osteoclast adhesion to bone slices, and later addition of high Ca(e) to the assay does not inhibit ongoing osteoclastic bone resorption.

Animals↗
PubMed1998

Osteoclastogenesis inhibitory factor (OCIF) directly inhibits bone-resorbing activity of isolated mature osteoclasts.

Osteoclastogenesis inhibitory factor (OCIF) was previously reported to specifically inhibit osteoclast development by interrupting the action of osteoclast differentiation factor (ODF), which is expressed in stromal cells and plays an important role in osteoclastogenesis. Here we report the direct action of OCIF on isolated rabbit mature osteoclasts to inhibit their functional bone-resorbing activity. The cell population employed in this study consisted of mature osteoclasts with more than 95% of purity. The inhibition by OCIF was dose dependent and observed as early as 6 h after the OCIF addition. An OCIF-binding protein of 140 kDa was detected on the plasma membrane of osteoclasts. ODF with a Mr of 40 kDa was recently isolated as a ligand for OCIF and shows to be identical to TRANCE/RANKL. However, ODF was not detected in osteoclasts. OCIF did not have any impact on the mRNA levels of cathepsin K/OC2 and carbonic anhydrase II responsible for degradation of organic and inorganic bone matrices, respectively, or on osteoclast apoptosis. However, OCIF reduced or disrupted the formation of F-actin ring in isolated osteoclasts, the cytoskeletal structure of which is correlated with bone resorption. These findings demonstrate that OCIF directly inhibits osteoclast function through an ODF-independent mechanism besides blocking the generation of osteoclasts.

Actins↗
PubMed2000

Osteoprotegerin ligand regulates osteoclast adherence to the bone surface in mouse calvaria.

The stimulators of bone resorption, prostaglandin E(2) (PGE(2)) and 1,25-dihydroxyvitamin D(3) (1,25D(3)), act through osteoblast-like cells to activate osteoclasts. One candidate for the intermediary produced by osteoblasts that subsequently stimulates the osteoclast is osteoprotegerin ligand (OPGL). OPGL has been shown to stimulate osteoclast differentiation and activation. The aim of the work reported here was to determine if soluble recombinant extracellular domain of human OPGL would bring about the change in osteoclast adhesion from the periosteum of mouse calvaria to the adjacent bone surface that occurs with the above-mentioned stimulators of resorption. This change in adherence or translocation of osteoclasts onto the bone surface required the expression and functioning of the integrin subunit, beta 3. We show that this soluble OPGL, like PGE(2) and 1,25D(3), stimulated the release of osteoclasts from the periosteum and their adherence to the bone surface accompanied by an increase in staining for immunolocalized integrin subunit beta 3. Recombinant human osteoprotegerin (OPG), which binds strongly to OPGL, inhibited this translocation of osteoclasts that occurred with PGE(2) and 1,25D(3), leaving integrin beta-3-negative osteoclasts on the periosteum. PGE(2) and 1,25D(3) increased the expression of messenger RNA for OPGL compared with indomethacin-treated controls after 6 h exposure. Evidence is presented that the change in the adhesion of osteoclasts from the periosteum to the bone surface, resulting in osteoclast activation, is mediated by OPGL.

Acid Phosphatase↗
PubMed1996

Effects of cadmium on osteoclast formation and activity in vitro.

Chronic exposure to cadmium has been linked to bone loss, low bone mass, and increased incidence of fracture. To determine if Cd could directly increase the formation of cells responsible for bone resorption, we cultured normal canine bone marrow cells containing the progenitor cells for osteoclasts. Cultures were evaluated for the number of multinucleate osteoclast-like cells (MNOCs) formed. Exposure to Cd (10-100 nM) increased the number of MNOCs formed over control values when cultured in the presence but not in the absence of a bone wafer. The MNOCs formed were functional, evidenced by pits excavated on the bone wafers included in the cultures. By 12 days, MNOCs formed in the presence of 50 nM Cd excavated significantly more pits and a greater pit area than did untreated MNOCs. By 14 days, the control values were similar to those of the Cd-exposed MNOCs, but pit formation was enhanced by Cd in that the ratio of pit complexes to single pits was increased twofold over that for untreated cultures. Mature osteoclasts, isolated from the long bones of rat neonates and cultured for 1-3 days on bone slices, provided a direct method to assess the effect of Cd on osteoclast activity. Exposure of osteoclast cultures to 100 nM Cd increased the number of osteoclasts present over that for untreated osteoclasts by a factor of 1.7 +/- 0.1, the number of pits excavated by 2.8 +/- 0.6, the area excavated by 3.2 +/- 0.8, and the area excavated per osteoclast by 1.8 +/- 0.4 (mean +/- SE; n = six experiments). These data suggest that Cd accelerates the differentiation of new osteoclasts from their progenitor cells and activates or increases the activity of mature osteoclasts.

Animals↗
PubMed1994

Osteoclast recruitment and modulation by calcium deficiency, fasting, and calcium supplementation in the rat.

In the rat, 1 week of a calcium-deficient diet will recruit large numbers of osteoclasts to long bone endosteal surfaces. Subsequent calcium supplementation causes the osteoclasts to disappear in 1-3 days but as little as 3 hours of calcium supplementation reduces the extent of their ruffled borders. To test the hypothesis that at some point there is an irreversible inhibition of osteoclasts, male, weanling, calcium-deficient, SD rats were given various amounts of calcium-containing diet followed by a 12-hour fast. No changes in seven morphological indices of osteoclast activity were found. The hypothesis that the fast had reversed the effects of the calcium diet was supported by a second experiment indicating that no inhibition threshold had been reached. Another experiment showed differences in the degree of osteoclast inhibition with different amounts of calcium supplementation, again without evidence of a threshold. These experiments raised two questions: (1) Will fasting recruit osteoclasts in calcium-replete rats? and (2) Is osteoclast recruitment facilitated by the presence of postosteoclasts? The results of experiments testing these hypotheses support the conclusion that fasting and calcium deficiency maintain plasma calcium levels by different mechanisms, and post-osteoclasts are not available for reactivation. It is concluded that inhibition of osteoclasts by dietary calcium is a graded phenomenon, and when osteoclasts have lost contact with the bone surface they are unavailable for reactivation; a threshold has been reached.

Analysis of Variance↗
PubMed1986

Histomorphometric analysis of osteoclastic bone resorption in metastatic bone disease from various primary malignomas.

The present study deals with qualitative und quantitative analysis of osteoclastic bone resorption in metastatic bone disease. 267 cases were examined histomorphologically and divided into three developmental stages. In the first 'phase of early appearance' no bone resorption takes place. The stimulation of osteoclastic resorption in the surroundings of tumour tissue is typical in the second 'phase of interaction'. Pressure atrophy, aseptic necrosis and osteolysis by the tumour cells themselves are other mechanisms of bone destruction in the last 'phase of carcinomatosis'. Because osteoclasts are exclusively responsible for the loss of bone tissue in the 'phase of interaction', this stage is suited for precise quantitative analysis of osteoclastic resorption. 24 pure osteolytic secondary bone tumours of various primary lesions were examined histomorphometrically. The numerical values were compared with each other and with standard values of healthy individuals. In contrast with normal bone tissue the fractional resorption surfaces und osteoclast indices increase in metastases. Activated osteoclasts are larger and have more nuclei. The numbers of osteoclast index and nuclei per osteoclast are significantly higher in renal than in breast carcinoma. Osteoclasts can be activated in distances of more than 500 micron from tumour tissue. The mean stimulation distance in metastasis from squamous cell carcinoma is markedly higher than in secondary bone tumours of breast carcinoma. Several osteoclast activating substances and divers mechanisms of stimulation might be responsible for different numerical values of morphometric parameters in metastases from various primary malignancies.

Bone Neoplasms↗
PubMed1988

Cytological and functional studies of preosteoclasts and osteoclasts in the alveolar bones from neonatal rats using microperoxidase as a tracer.

Microperoxidase (MP) was used to investigate the cytological and functional features of preosteoclasts and osteoclasts during rat alveolar bone development. We observed mononuclear cells as preosteoclasts and multinuclear cells with and without ruffled borders (RB). In the bone facing multinuclear cells with RB as active osteoclasts, MP was extensively deposited along the external bone matrix undergoing resorption, and was phagocytosed with bone components into the vacuoles of osteoclasts. Neither preosteoclasts nor multinuclear cells without RB took up MP and bone components. Only multinuclear cells with RB seemed to resorb bone. Monocytes/macrophages (MMP) phagocytosed MP through all regions of the plasma membrane, whereas osteoclasts took up MP only through the RB which was a part of the plasma membrane. Endogenous peroxidase was detected in the MMP but not in preosteoclasts and osteoclasts. Thus, osteoclasts were considerably different from the MMP. The numbers of MMP were extremely few close to the osteoclasts, whereas moderate numbers of preosteoclasts were located close to the osteoclasts. Except for the nucleus and RB, there were many morphological similarities between preosteoclasts and osteoclasts. We therefore suggest that preosteoclasts, rather than MMP, are the precursors of osteoclasts during alveolar bone development of neonatal rats.

Alveolar Process↗
PubMed1992

Identification of osteopontin in isolated rabbit osteoclasts.

Bone remodeling is a complex process coupling bone formation and resorption. Osteoblasts, the bone-forming cells, are known to produce various bone matrix proteins and cytokines; however, little is known about protein factors produced by osteoclasts or bone-resorbing cells. A method utilizing the high affinity of osteoclasts for tissue culture dishes was developed to isolate a large number of pure osteoclasts from rabbit long bones. A cDNA library was then constructed from these isolated osteoclasts, and differential cDNA screening was performed between osteoclasts and spleen cells. Two clones representing osteoclast-specific clones, named OC-1 and OC-2, were isolated. By Northern blot analysis, OC-1 was expressed in osteoclasts and in kidneys, whereas OC-2 was specific for osteoclasts. OC-1 was found to encode osteopontin from its nucleotide sequence, and therefore, osteopontin may have other functions for osteoclastic bone resorption besides osteoclast attachment to bone.

Amino Acid Sequence↗
PubMed1996

Calcitonin promotes osteoclast survival in vitro.

Inactivation of resorbing osteoclasts by calcitonin is associated with typical morphological changes and alteration of the specific organization of osteoclast cytoskeleton. Here we show that calcitonin also promotes the survival of rat osteoclasts in vitro, cultured either on glass or bone, by delaying the onset of apoptosis. Parathyroid hormone had no effect on osteoclasts cultured on glass but it slightly increased apoptosis index of osteoclasts cultured on bone. Calcitonin was also able to rescue osteoclasts in calvarial explant cultures. The survival effect of calcitonin was mimicked by dibutyryl cAMP and could not be blocked by various metabolic inhibitors known to affect the apoptotic pathway. However, clodronate-induced apoptosis of osteoclasts could not be reversed by calcitonin and neither could calcitonin rescue osteoclasts already committed to apoptosis. It did not alter the distribution of Bcl-2 in osteoclasts. Our results show that at least in vitro calcitonin protects osteoclasts from apoptosis and suggest that it regulates the onset of apoptosis.

Animals↗
PubMed1988

Role of mineralizing cartilage in osteoclast and osteoblast recruitment.

Periost-free, live and/or devitalized cartilaginous long bone rudiments of fetal mice were transplanted under the renal capsule of adult syngeneic mice to study the role of cells and intercellular matrix in the recruitment and formation of osteoclasts and osteoblasts, both identified by means of enzyme- and immunohistochemical methods. Live bone rudiments recruited host-derived osteoclasts within 5 days after transplantation. Osteoblasts developed as rapidly as osteoclasts and participated in the modeling of the rudiments into hemopoietic bone marrow containing ossicles. Devitalized bone rudiments, killed before osteoclastic invasion had occurred, did not recruit osteoclasts or osteoblasts, and were not resorbed up till 35 days after transplantation. Co-transplantation of live and devitalized bone rudiments however resulted in osteoclastic resorption of the killed rudiments, starting 9 days after transplantation. Again the live rudiments were modeled into ossicles. Devitalized bone rudiments which had been invaded by osteoclasts before killing and transplantation, did recruit host osteoclasts, but at a slower rate than live rudiments, and depending on the number of resorption sites at the time of transplantation. Osteoblasts were not formed. These data suggest that in developing long bones chondrocyte activity is involved in the recruitment of osteoclasts as well as osteoblasts. Matrix components diffusing from resorbing surfaces seem to be involved in osteoclast recruitment.

Acid Phosphatase↗
PubMed1988

A morphologic study of osteoclasts isolated from osteopetrotic microphthalmic (mi/mi) mouse and human fetal long bones using an instrument permitting combination of light and scanning electron microscopy.

Cell surface structures of isolated osteopetrotic (mi/mi) and normal murine (+/+ and +/mi) and human osteoclasts were examined in a microscope combining light and scanning electron microscopy (LM/SEM). Tartrate-resistant acid phosphatase (TrAP) was used as an histochemical osteoclast marker. In osteopetrotic bone, as in normal murine bone, TrAP activity was exclusively seen in osteoclasts and preosteoclasts and was therefore judged a suitable marker for identification of isolated osteoclasts. A method was developed for preparation of LM/SEM specimens from osteoclast-enriched cell suspensions. In the LM/SEM isolated osteoclasts were easily recognized in the LM mode by TrAP contents. In specimens prepared from murine cells, but not human cells, LM identification of osteoclasts by TrAP was essential. This was in particular true for small, mononuclear, mi/mi osteoclasts. All osteoclasts examined had a villous appearance and were well spread over the glass substrate. There were no differences in cell surface morphology and in adherence to glass between osteopetrotic and normal osteoclasts.

Acid Phosphatase↗
PubMed2005

Mechanism of osteoclast mediated bone resorption--rationale for the design of new therapeutics.

Bone resorption is an important cellular function in the development and physiology of the skeleton. Pathophysiology of several skeletal diseases includes either increased (for instance osteoporosis, metastatic bone disease and Paget's disease of bone) or decreased (various syndromes of osteopetrosis) bone resorption rate. Thus there is a genuine need to regulate, especially inhibit, bone resorption rate in several diseases. Bone resorption can be inhibited by several strategies. One can prevent osteoclast formation, inhibit their action or induce premature cell death. All these strategies have been used in pharmacology to inhibit bone resorption and there are also physiological regulators for each of these three different phases of in osteoclast life. Many present resorption inhibitors inhibit osteoclast formation via osteoblastic cells since they are producing a number of factors that are essential for osteoclast differentiation. Best characterized of these factors are macrophage colony stimulating factor (M-CSF) and receptor activator of NFêB ligand (RANKL). For instance sex steroids, parathyroid hormone and some interleukins are known to exert their positive or negative effects on osteoclast differentiation via the RANK/RANKL/osteoprotegrin pathway. It is not yet clear enough how specific intervention to osteoclast formation is since also other cell lineages derived from hematopoetic precursors use similar signalling pathways. An effective inhibition of bone resorption can also be achieved by inhibiting osteoclast activity to resorb bone. Examples of this category of physiological and pharmacological inhibitors are calcitonin and aminobisphosphonates, respectively. Finally one can reduce bone resorption by shortening osteoclast lifespan with substances that induce apoptosis in osteoclasts. A good example of these substances is a first generation bisphosphonate, clodronate. Several new potential molecular targets have been revealed during recent years since many individual molecules in osteoclast differentiation, function and apoptosis have been identified and their physiological functions revealed. Thus we are expecting several new bone inhibitors to be developed in following years both for experimental studies and finally also for clinical use.

Apoptosis↗