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PubMed2003

Role of parathyroid hormone in mediating age-related changes in bone resorption in men.

Osteoporosis in men is an important and growing public health problem. While there has been extensive work done on defining the mechanism(s) of the age-related increase in bone resorption in women, our knowledge regarding the pathogenesis of bone loss in elderly men is still incomplete. We previously demonstrated that the age-related increase in serum PTH contributes substantially to the increased bone resorption in elderly women, since suppression of PTH levels by an intravenous calcium infusion decreased bone resorption markers to a greater extent in elderly compared to premenopausal women. In the present study, we tested the hypothesis that the comparable increase in PTH levels in elderly men (age 70-78 years) was driving bone resorption to a greater extent in these men than in younger men (age 40-50 years). PTH secretion was suppressed by an intravenous calcium infusion and the corresponding changes in the bone resorption marker, urine N-telopeptide of type I collagen (NTx) were assessed. In contrast to our previous findings in pre- versus postmenopausal women, suppression of PTH secretion in elderly men did not result in a greater decrease in urine NTx excretion than in the younger men (change in NTx excretion in the elderly men, -2.79+/-1.99 nmol/mmol Cr, versus that in the younger men, -5.07+/-1.39 nmol/mmol Cr, P=0.356). Collectively, these data suggest that the relationship between the age-related increase in serum PTH levels and bone resorption differs between elderly men and women. Since both estrogen and testosterone can attenuate the bone resorbing effects of PTH, it is possible that this difference may be due to the much milder degree of sex steroid deficiency in elderly men as compared to postmenopausal women.

Adult↗

PubMed1993

Possible variation in bone resorption during the normal menstrual cycle.

In order to determine whether bone turnover varies during the normal menstrual cycle, we measured biochemical markers of bone resorption (serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (sICTP), fasting urinary hydroxyproline/creatinine, fasting urinary pyridinoline/creatinine and fasting urinary deoxypyridinoline/creatinine) and bone formation (plasma osteocalcin, serum carboxy-terminal propeptide of type I procollagen and serum alkaline phosphatase) in ten healthy premenopausal women every two or three days for a complete menstrual cycle. A cyclic pattern was detected in sICTP, with its nadir during the follicular phase and its peak during the luteal phase, and an overall variation of 17% during the menstrual cycle (p = 0.004). No cyclic changes were observed in the urinary parameters of bone resorption or in the biochemical markers of bone formation. We conclude that sICTP, a new biochemical marker of bone resorption, undergoes small variations during a normal menstrual cycle in premenopausal women, whereas the biochemical markers of bone formation remain constant.

Adult↗

PubMed1999

A role for interleukin-6 in parathyroid hormone-induced bone resorption in vivo.

Parathyroid hormone (PTH) exerts its regulatory effects on calcium homeostasis in part by stimulating the release of calcium from the skeleton. PTH stimulates bone resorption indirectly, by inducing the production by stromal/osteoblastic cells of paracrine agents which recruit and activate the bone-resorbing cell, the osteoclast. The identity of the stromal cell/osteoblast-derived paracrine factor(s) responsible for mediating the effects of PTH on osteoclasts is uncertain. Recently, it has been demonstrated that the cytokine interleukin-6 (IL-6), which potently induces osteoclastogenesis, is produced by osteoblastic cells in response to PTH. Further, we have reported that circulating levels of IL-6 are elevated in patients with primary hyperparathyroidism, and correlate with biochemical markers of bone resorption. Thus, IL-6 may play a permissive role in PTH-induced bone resorption. In the current studies, we demonstrate that low-dose PTH infusion in rodents increased serum levels of IL-6, coincident with a rise in biochemical markers of bone resorption. In mice, both acute neutralization and chronic deficiency of IL-6 were associated with markedly lower levels of biochemical markers of bone resorption in response to PTH infusion than were observed in animals with normal IL-6 production. Acute neutralization of IL-6 did not affect PTH-induced changes in markers of bone formation. These findings demonstrate that PTH regulates systemic levels of IL-6 in experimental animals, that IL-6 is an important mediator of the bone-resorbing actions of PTH in vivo and suggest that IL-6 plays a role in coupling PTH-induced bone resorption and formation.

Animals↗

PubMed2001

Effects of short-term use of ibuprofen or acetaminophen on bone resorption in healthy men: a double-blind, placebo-controlled pilot study.

Prostaglandins are known to be involved in the metabolism of bone, having a significant influence on bone resorption in cases of bone pathology. We therefore investigated the short-term effects of two commonly used nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and acetaminophen (paracetamol), on bone resorption in healthy men. In a randomized, double-blind pilot study, 28 healthy, age- and weight-matched male volunteers were treated with ibuprofen (n = 10), acetaminophen (n = 9), or a placebo (n = 9) for 3 days. As an indication of bone resorption rate, levels of the biochemical bone markers N-telopeptide (NTx) and free deoxypyridinoline (D-Pyr) were measured in urine. Differences in resorption marker levels pre- and post-NSAID use were then compared between groups. We found that NTx concentrations in the acetaminophen group were lower than placebo (p = 0.048), whereas NTx levels in the ibuprofen group were higher than in the acetaminophen group (p = 0.016). By contrast, D-Pyr concentrations in the ibuprofen group were significantly lower than in the placebo group (p = 0.009). A comparison of the percentage changes of D-Pyr:NTx ratios found that the ratio in the ibuprofen group was significantly lower than that of both the control (p = 0.0065) and acetaminophen (p = 0.01) groups. These results show the differential effects of ibuprofen and acetaminophen on urinary excretion of peptide-bound and free deoxypyridinoline cross-links of type I collagen. Short-term ibuprofen use may alter the renal handling of collagen cross-links and increase bone resorption to a greater extent than acetaminophen in normal men.

Acetaminophen↗

PubMed2000

Activin release from bone coupled to bone resorption in organ culture of neonatal mouse calvaria.

Activin, a member of the transforming growth factor-beta (TGF-beta) superfamily, is present in the bone matrix and assumed to be involved in the regulation of bone formation. In the present study, we investigated whether the release of activin from bone is coupled with bone resorption. Neonatal mouse calvaria were cultured in the presence of various stimulators of bone resorption (parathyroid hormone [PTH], interleukin-1beta, prostaglandin E2) for up to 72 h, and the activin activity in the medium was measured using a specific bioassay for activin. Activin activity was accumulated in proportion to the time- and dose-dependent increase in calcium release from bone into the medium (bone resorption). An inhibition of PTH-dependent bone resorption by a bisphosphonate, disodium dichlormethane-1,1-bisphosphonic acid (Cl2MBP), completely blocked release of activin activity from bone into the medium. In primary culture of calvarial cells, however, neither PTH nor Cl2MBP affected activin production. These findings indicate that release of activin activity from bone tissue is strongly coupled to bone resorption. Because activin possesses osteogenic activities, activin released locally from bone might be involved in the regulation of bone formation in the physiological process of bone remodeling, as has been suggested for TGF-beta.

Activins↗

PubMed2000

Specific antagonists of NMDA receptors prevent osteoclast sealing zone formation required for bone resorption.

N-Methyl-d-aspartate (NMDA) glutamate receptors, widely distributed in the nervous system, have recently been identified in bone. They are expressed and are functional in osteoclasts. In the present work, we have studied the effects of specific antagonists of NMDA receptors on osteoclast activation and bone resorption. Using an in vitro assay of bone resorption, we showed that several antagonists of NMDA receptors binding to different sites of the receptor inhibit bone resorption. Osteoclast activation requires adhesion to the bone surface, cytoskeletal reorganization and survival. We demonstrated by autoradiography that the specific NMDA receptor channel blocker, MK 801, binds to osteoclasts. This antagonist had no effect on osteoclast attachment to bone and did not induce osteoclast apoptosis. In contrast, MK 801 rapidly decreased the percentage of osteoclasts with actin ring structures that are associated with actively resorbing osteoclasts. These results suggest that NMDA receptors expressed by osteoclasts may be involved in adhesion-induced formation of the sealing zone required for bone resorption.

Actins↗

PubMed1987

Characterization of adenosine receptors in bone. Studies on the effect of adenosine analogues on cyclic AMP formation and bone resorption in cultured mouse calvaria.

The effect of different adenosine analogues on cyclic AMP (cAMP) formation and bone resorption in cultured mouse calvarial bones was investigated. 5'-N-ethylcarboxamidoadenosine (NECA), R-N6-phenylisopropyl-adenosine (PIA), N6-cyclohexyl-adenosine (CHA) and 2-chloroadenosine all stimulated cyclic AMP formation with a threshold close to 1 mumol l-1); NECA was the most potent agonist. Theophylline (10, 100 mumol l-1) inhibited the cAMP accumulation induced by NECA and 2-chloroadenosine (30 and 300 mumol l-1), dose dependently. There was no inhibition of cAMP formation by PIA and CHA in forskolin-treated bone tissue. SQ 22, 536 and 2',5'-dideoxyadenosine (100 mumol l-1) both inhibited rolipram-stimulated cAMP formation. Cyclic AMP accumulation in isolated osteoblast-like cells from neonatal mouse calvarial bones was stimulated by NECA (10 and 100 mumol l-1) and 2-chloroadenosine (100 mumol l-1). 2-chloroadenosine (10 and 30 mumol l-1), but not NECA, PIA nor CHA, caused a dose-dependent stimulation of 45Ca release in both 48- and 120-h culture. The effect of 2-chloroadenosine on 45Ca release could not be antagonized by theophylline. Neither NECA, PIA, CHA nor 2-chloroadenosine could affect PTH-stimulated 45Ca release in short term cultures (6, 24 h). By contrast, stimulation of cAMP formation by forskolin or dibutyryl cAMP caused a rapid (6 h) inhibition of PTH-stimulated bone resorption. The results demonstrate functional A2 and P-site receptors in mouse calvaria and osteoblast-like cells, but no A1-receptor was detected. These adenosine receptors regulate cAMP, but are not intimately linked to bone resorption. The calcium mobilization induced by 2-chloroadenosine appears to be unrelated to adenosine receptors.

2-Chloroadenosine↗

PubMed1985

Inhibition of bone resorption in vitro by compound 48/80.

The mechanisms that control cycles of bone formation and bone resorption are not well understood. In this report we provide evidence that compound 48/80 is a potent inhibitor of bone resorption in vitro. Resorption was assessed by the release of calcium-45 from pre-labelled newborn mouse calvaria that were treated with compound 48/80 and/or parathyroid hormone (PTH) in organ culture. Our results demonstrate that co-incubation of calvaria with PTH plus compound 48/80 (concentrations 1-10 mcg/ml) produces a marked reduction of calcium-45 release compared to PTH alone. Furthermore, pre-incubation of calvaria with compound 48/80, for as little as three hours, inhibits resorption by subsequent treatment with PTH alone. Measurement of lactate dehydrogenase (LDH) released into the culture medium indicated that treatment with compound 48/80, at the doses and time periods studied, was not cytotoxic. This novel effect of compound 48/80 may provide a useful tool for studying the cellular mechanisms involved in the bone resorption process.

Animals↗

PubMed2002

Development of a synthetic peptide-based tartrate-resistant acid phosphatase radioimmunoassay for the measurement of bone resorption in rat serum.

Selective markers of bone turnover provide a convenient and reproducible alternative to the complex and expensive histochemical techniques used commonly to study the effect of pharmacological agents and the pathogenesis of bone disease in the ovariectomized (OVX) rat model. One marker, which has been specifically linked to terminally differentiated osteoclasts and, thus, provides useful insight at cellular levels, is type-5 tartrate-resistant acid phosphatase (TRACP). We describe the development of a TRACP radioimmunoassay (RIA), which requires synthetic peptide for antibody development. To develop the RIA, polyclonal antibodies were generated in goats against a synthetic peptide, DPSVRHQRKCY, corresponding to amino acid residues 267-275 of the rat type-5 TRACP sequence. In the RIA, 50 microl of rat serum, 100 microl of goat anti-TRACP antibodies, and 100 microl of tracer were incubated overnight. The antibody-bound fraction was separated, counted, and unknown values were calculated by comparison with the peptide calibrator. Rat serum shows parallelism with the synthetic peptide calibrator used in the RIA. The sensitivity of the RIA was 24.7 microg/l, and the measuring range was 19-2476 microg/l. The average intra-assay coefficients of variation for (CV) two controls were less than 7%. The average dilution and spike recoveries were 107% and 87%, respectively. We applied our peptide-based RIA to study bone resorption in an OVX rat model. TRACP concentrations in serum in 12-week-old OVX Sprague Dawley rats were 14%-22% (P < 0.05) higher than those in the sham-operated rats, and TRACP concentrations in OVX rats treated with estradiol were 24%-32% lower (P < 0.01) than those in the vehicle-treated OVX group. Similarly, as compared with those in OVX rats, TRACP concentrations decreased to those of sham levels in OVX rats receiving 10 microg/kg per day of alendronate for 10 days. In addition, the TRACP levels determined by RIA showed a significant correlation with serum C-telopeptide (type-I collagen) concentrations (r = 0.56; P < 0.001) measured by an enzyme-linked immunosorbent assay (ELISA) developed earlier for the rat model. In conclusion, we have developed a TRACP RIA that could be used to monitor the rate of bone resorption in the rat model.

Acid Phosphatase↗

PubMed1996

Transforming growth factor-beta stimulates bone resorption in neonatal mouse calvariae by a prostaglandin-unrelated but cell proliferation-dependent pathway.

The relationships between bone resorption, prostanoid formation, and cell proliferation in cultured neonatal mouse calvariae stimulated with transforming growth factor-beta (TGF-beta) have been examined. Bone resorption was assessed by analyzing the mobilization of minerals (45Ca, Ca2+., Pi) and the release of 3H from bones prelabeled with [3H]proline. Prostanoid formation was determined by analyzing the amounts of prostaglandin E2 (PGE2) and 6-keto-prostaglandin F1 alpha (the stable breakdown product of PGI2) in culture media. Purified porcine TGF-beta 1 and recombinant human TGF-beta 2 stimulated the release of 45Ca and the formation of prostanoids. The effects were time and dose dependent. The concentrations of TGF-beta 1 and TGF-beta 2 causing half maximal stimulation of 45Ca release were 1 and 0.1 ng/ml, respectively. TGF-beta 1 also enhanced the release of 3H from [3H]proline labeled bones and the mobilization of Ca2+ and Pi from unlabeled bones, as well as the release of lysosomal enzymes (beta-N-acetylglucosaminidase). The degree of stimulation of mineral mobilization and matrix degradation was less than that obtained in bones stimulated with parathyroid hormone or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). TGF-beta 1-induced stimulation of 45Ca release was inhibited by calcitonin, acetazolamide, and the biphosphonate AHPrBP, three different osteoclast inhibitors. In contrast to the escape from calcitonin-induced inhibition seen in parathyroid hormone (PTH)-stimulated bones, the inhibitory effect of calcitonin in TGF-beta 1-stimulated bones persisted in long-term cultures (144 h). The stimulatory effect of TGF-beta 1 was inhibited by anti-TGF-beta 1 and by gamma-interferon (1000 U/ml). Indomethacin (1 microM), flurbiprofen (1 microM), and meclofenamic acid (1 microM) completely abolished the stimulatory effect of TGF-beta 1 on PGE2 and 6-keto-PGF 1 alpha formation without affecting TGF-beta 1-induced stimulation of 45Ca release. Similarly, the stimulatory effect of TGF-beta 2 on 45Ca release was unaffected by indomethacin. In bones in which prostaglandin formation was abolished by indomethacin, a 45Ca release response to TGF-beta 1 was obtained at 12 h. The mitotic inhibitor hydroxyurea inhibited TGF-beta 1 but not PTH-induced 45Ca release. These data demonstrate that TGF-beta 1 and TGF-beta 2 have the capacity to stimulate bone resorption and prostanoid formation in neonatal mouse calvariae, but that the effect of TGF-beta on bone resorption is unrelated to prostanoid formation. In addition, it is shown that bone resorption stimulated by TGF-beta is dependent on cell replication.

Acetylglucosaminidase↗

PubMed1995

Triiodothyronine potentiates the stimulatory effects of interleukin-1 beta on bone resorption and medium interleukin-6 content in fetal rat limb bone cultures.

It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5,3'-triiodothyronine (T3) on bone resorption (45Ca release) and on the IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T3 alone increased 45Ca release significantly only at a fairly high concentration (10(-6)M) under the conditions used. T3 alone, over a 10(-11)-10(-6) M concentration range, failed to elicit a detectable effect on the medium IL-6 content. However, T3 potentiated the stimulatory effect of interleukin-1 beta (IL-1 beta) on IL-6 production in a dose-dependent manner. T3, 10(-8) M, also significantly increased IL-1 beta-stimulated calcium release. Inhibition of IL-1 beta with 1 muM interleukin-1 receptor antagonist (IL-1ra) abrogated the potentiating effects of T3 on IL-1 beta-stimulated IL-6 production and blocked the combined effect of T3 and IL-1 beta on 45Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL-1 beta, as well as the combined effect of IL-1 beta and T3 on resorption and IL-6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 microM prostaglandin E1 (PGE1) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1 beta, T3 increased bone resorption at much lower concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed2006

Reveromycin A, an agent for osteoporosis, inhibits bone resorption by inducing apoptosis specifically in osteoclasts.

Mature bone-resorbing osteoclasts (OCs) mediate excessive bone loss seen in several bone disorders, including osteoporosis. Here, we showed that reveromycin A (RM-A), a small natural product with three carboxylic groups in its structure, induced apoptosis specifically in OCs, but not in OC progenitors, nonfunctional osteoclasts, or osteoblasts. RM-A inhibited protein synthesis in OCs by selectively blocking enzymatic activity of isoleucyl-tRNA synthetase. The proapoptotic effect of RM-A was inhibited by neutralization or disruption of the acidic microenvironment, a prominent characteristic of OCs. RM-A was incorporated in OCs but not in nonfunctional osteoclasts and OC progenitors in neutral culture medium. Effects of RM-A on OC apoptosis increased under acidic culture conditions. RM-A not only was incorporated, but also induced apoptosis in OC progenitors in acidic culture medium. RM-A inhibited osteoclastic pit formation, decreased prelabeled (45)Ca release in organ cultures, and antagonized increased bone resorption in ovariectomized mice. These results suggested that preventive effects of RM-A on bone resorption in vitro and in vivo were caused by apoptosis through inhibition of isoleucyl-tRNA synthetase in OCs and that specific sensitivity of OCs to RM-A was due to the acidic microenvironment, which increased cell permeability of RM-A by suppressing dissociation of protons from carboxylic acid moieties, making them less polar. This unique mechanism suggested that RM-A might represent a type of therapeutic agent for treating bone disorders associated with increased bone loss.

Acids↗

PubMed2001

Titanium particles stimulate bone resorption by inducing differentiation of murine osteoclasts.

BACKGROUND: Loosening of orthopaedic implants is mediated by cytokines that elicit bone resorption and are produced in response to phagocytosis of implant-derived wear particles. This accelerated bone resorption could be due to increased osteoclastic activity, survival, or differentiation. Although a number of in vitro studies have shown that wear particles increase osteoclastic activity, the increase was less than twofold in all cases. The objective of the current study was to test the hypothesis that wear particles stimulate bone resorption by inducing osteoclast differentiation. METHODS: Conditioned media were prepared from murine marrow cells or human peripheral blood monocytes incubated in the presence or absence of titanium particles. The effects of conditioned media on osteoclast differentiation were examined with use of a recently developed assay in which osteoclast precursors are co-cultured with mesenchymal support cells. RESULTS: The present study showed that titanium particles induced both murine marrow cells and human peripheral blood monocytes to produce factors that stimulated osteoclast differentiation. The mean increase in osteoclast differentiation was 29.3+/-9.4-fold. The stimulation of osteoclast differentiation led to a parallel increase in bone resorption. The amount of stimulation was regulated in a dose-dependent manner by the concentration of both titanium particles and conditioned media. The stimulation of osteoclast differentiation required interactions between the cells and the particles themselves and, therefore, was not due to metal ions, soluble contaminants released from the particles, or submicrometer particles. In contrast, conditioned media from control cells incubated in the absence of titanium particles had no detectable effect on any of the examined parameters. CONCLUSIONS: The present study showed that titanium particles stimulate in vitro bone resorption primarily by inducing osteoclast differentiation. In contrast, the titanium particles had only small effects on osteoclast activity or survival.

Adult↗

PubMed2001

Effect of interleukin-17 on nitric oxide production and osteoclastic bone resorption: is there dependency on nuclear factor-kappaB and receptor activator of nuclear factor kappaB (RANK)/RANK ligand signaling?

Interleukin-17 (IL-17) is a proinflammatory cytokine produced exclusively by activated memory T cells and has recently been found to stimulate osteoclastic resorption. Like other proinflammatory cytokines, IL-17 may affect osteoclastic bone resorption indirectly via osteoblasts, possibly by mechanisms previously reported for chondrocytes that respond in very similarly to osteoblasts. As in chondrocytes, but only in combination with tumor necrosis factor-alpha (TNF-alpha), IL-17 induced nitric oxide (NO) production in osteoblastic cells and fetal mouse metatarsals by a nuclear factor-kappaB (NF-kappaB)-dependent mechanism. This effect was associated with elevated mRNA levels of the NF-kappaB isoforms RelA and p50. In fetal mouse metatarsals, IL-17 stimulated osteoclastic bone resorption only in combination with TNF-alpha. The pathway by which the cytokine combination exerts this effect was examined using inhibitors of NO synthesis and NF-kappaB activation. Although both inhibitors used abolished NO production, they did not prevent the stimulatory effect of the cytokine combination on osteoclastic resorption. In contrast, the inhibitors slightly increased osteoclastic resorption, suggesting a suppressive rather than stimulatory effect of NO on cytokine-induced bone resorption. In addition, we showed that IL-17 + TNF-alpha stimulated osteoclastic resorption independent of NF-kappaB signaling. To further examine the pathway by which osteoclastic resorption was stimulated, we used osteoprotegerin, a specific inhibitor of the receptor activator of NF-kappaB (RANK)/receptor activator of the NF-kappaB ligand (RANKL) pathway. Osteoprotegerin partially inhibited IL-17 + TNF-alpha-stimulated osteoclastic resorption only at the high concentration of 1000 ng/mL, whereas it completely blocked parathyroid hormone-related peptide-stimulated resorption at 300 ng/mL. In conclusion, IL-17 stimulated NO production by an NF-kappaB-dependent pathway in osteoblastic cells and fetal mouse metatarsals only in combination with TNF-alpha. Neither NO production nor NF-kappaB signaling, and only partly the RANK/RANKL pathway, were involved in the stimulatory effect of the cytokine combination on osteoblastic bone resorption in these long bones, suggesting the existence of other pathways by which osteoclastic resorption can be stimulated.

3T3 Cells↗

PubMed1989

[Bone resorption in orthodontic tooth movement: an attempted schematization].

The osteoclast is the major cellular agent of bone resorption. Hormonal stimulation of bone resorption is indirect and depends on the osteoblastic function. Protease production is the final common pathway through which osteoblastic cells initiate osteoclastic resorption. Exposition of the mineralised matrix and contact with the osteoclasts always comes before resorption, regardless of the stimulating agent involved in the resorption process. In orthodontic conditions, production and activation of osteoclasts may be attained through different ways. Inflammation subsequent to tissue damage and bioelectric perturbations associated to alveolar bending can be considered as two major events which may lead to increase bone resorption and orthodontic tooth displacement. The precise transduction mechanism of an orthodontic force into cellular resorbing activity is still obscure.

Alveolar Process↗

PubMed1986

Effect of phenytoin on rat bone resorption in vitro.

Effects of phenytoin (DPH) on parathyroid hormone (PTH)- and 1,25-dihydroxyvitamin D3(1,25DHCC)-mediated bone resorption in bone organ culture were evaluated: it markedly inhibited the actions of both. However, PTH tended to overcome the initial effects of DPH, whereas bone resorption due to 1,25DHCC remained depressed as if DPH treatment had continued. Thus DPH-induced bone abnormalities may involve a greater direct effect on 1,25DHCC regulation of bone homeostasis than on PTH.

Animals↗

PubMed2000

Role of transcriptional factor activation protein-1 in endogenous expression of the interleukin-1 beta gene involved in Porphyromonas gingivalis fimbria-stimulated bone resorption in the mouse calvarial system.

We previously suggested that endogenous interleukin-1 beta (IL-1 beta) produced by Porphyromonas gingivalis fimbriae stimulation in calvarial bone cell cultures plays a role in bone resorption as a major cytokine. Therefore, in the present study, we initiated experiments to clarify the stimulatory mechanism of IL-1 beta gene expression in fimbria-stimulated bone resorption. Fimbria-stimulated bone resorption was dramatically inhibited by curcumin, a potent inhibitor of activation protein-1 (AP-1). In fact, the fimbriae induced markedly both the expression of c-fos and c-jun genes and their protein production in the calvarial cells. In addition, a mixture of antisense oligonucleotides against c-fos and c-jun significantly inhibited not only the fimbria-induced expression of the IL-1 beta gene but also the fimbria-induced bone resorption. Therefore, the present study demonstrates that transcriptional factor AP-1 plays a functional role in P. gingivalis fimbria-stimulated bone resorption via endogenous IL-1 beta in the mouse calvarial system.

Animals↗

PubMed1988

[Periosteal bone resorption in the area of the metaphysis of growing bone as a precursor of epiphyseal injuries. A polarization optical and scanning electron microscopy study].

Macerated epiphyses of the growing infant bone exhibit an irregular surface which can already be observed at the macroscopic level. Polarizing microscopy demonstrates extended zones of bone resorption on the cortical surface, deductable from numerous lacunae of Howship. Ensuing experimentally induced epiphysiolyses, cortical bone fragments adhering to the inner surface of the periosteum are demonstrable by scanning electron microscopy. Having been torn out of the bone together with the periosteum, these cortical fragments leave corresponding defects on the bone surface. Due to the remodelling of the bone, involving the readjustment of the shape of the extremity, the attachment of the periosteum is relatively poor in the metaphyseal region of the growing bone. The influence of pathological forces can therefore easily cause a detaching of the periosteum in this region. The latter results in a significant weakening of the epiphyseal fastening in the zone between the epiphyseal plate and the metaphysis. The patterns of injury in the region of the growth plate are therefore essentially determined by the varying attachment of the periosteum to the metaphysis.

Adolescent↗