MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts' differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

• Klíčová slova
• differentiation, miR-21-5p, osteoblasts, osteoclasts, osteogenesis, precursor cells,
• MeSH
• buněčná diferenciace genetika   MeSH
• buněčné linie MeSH
• extracelulární matrix metabolismus   MeSH
• kokultivační techniky MeSH
• kyselá fosfatasa rezistentní k tartarátu metabolismus   MeSH
• messenger RNA genetika   MeSH
• mikro RNA genetika   metabolismus   MeSH
• myši MeSH
• osteoblasty metabolismus   MeSH
• osteogeneze genetika   MeSH
• osteoklasty metabolismus   MeSH
• osteopontin genetika   metabolismus   MeSH
• parakrinní signalizace genetika   MeSH
• protein PEBP2alfaA genetika   metabolismus   MeSH
• resorpce kosti metabolismus   MeSH
• signální transdukce genetika   MeSH
• transfekce MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Acp5 protein, mouse MeSH Prohlížeč
• kyselá fosfatasa rezistentní k tartarátu MeSH
• messenger RNA MeSH
• mikro RNA MeSH
• MIRN21 microRNA, mouse MeSH Prohlížeč
• osteopontin MeSH
• protein PEBP2alfaA MeSH
• Runx2 protein, mouse MeSH Prohlížeč
• Spp1 protein, mouse MeSH Prohlížeč

OBJECTIVE: Aseptic loosening (AL) is the most frequent long-term reason for revision of total knee arthroplasty (TKA) affecting about 15-20% patients within 20 years after the surgery. Although there is a solid body of evidence about the crucial role of inflammation in the AL pathogenesis, scared information on inflammation signature and its time-axis in tissues around TKA exists. DESIGN: The inflammation protein signatures in pseudosynovial tissues collected at revision surgery from patients with AL (AL, n = 12) and those with no clinical/radiographic signs of AL (non-AL, n = 9) were investigated by Proximity Extension Assay (PEA)-Immunoassay and immunohistochemistry. RESULTS: AL tissues had elevated levels of TNF-family members sTNFR2, TNFSF14, sFasL, sBAFF, cytokines/chemokines IL8, CCL2, IL1RA/IL36, sIL6R, and growth factors sAREG, CSF1, comparing to non-AL. High interindividual variability in protein levels was evident particularly in non-AL. Levels of sTNFR2, sBAFF, IL8, sIL6R, and MPO discriminated between AL and non-AL and were associated with the time from index surgery, suggesting the cumulative character of inflammatory osteolytic response to prosthetic byproducts. The source of elevated inflammatory molecules was macrophages and multinucleated osteoclast-like cells in AL and histiocytes and osteoclast-like cells in non-AL tissues, respectively. All proteins were present in higher levels in osteoclast-like cells than in macrophages. CONCLUSIONS: Our study revealed a differential inflammation signature between AL and non-AL stages of TKA. It also highlighted the unique patient's response to TKA in non-AL stages. Further confirmation of our preliminary results on a larger cohort is needed. Analysis of the time-axis of processes ongoing around TKA implantation may help to understand the mechanisms driving periprosthetic bone resorption needed for diagnostic/preventative strategies.

• MeSH
• cytokiny metabolismus   MeSH
• histiocyty metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makrofágy metabolismus   patologie   MeSH
• osteoklasty metabolismus   patologie   MeSH
• reoperace MeSH
• resorpce kosti komplikace   metabolismus   patofyziologie   chirurgie   MeSH
• selhání protézy škodlivé účinky   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• totální endoprotéza kolene škodlivé účinky   MeSH
• zánět komplikace   metabolismus   patofyziologie   chirurgie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH

Alcohol use has been identified as a risk factor for the development of osteoporosis. Eight male Wistar rats at two months of age were alcoho-fed (7.6 g 95 % ethanol/kg b.w. per day) to evaluate the effects of long-term administration (three months) of alcohol in drinking water. We have used a dose which is considered to be comparable to a dose of 1 liter of wine or 2.5 liters of 12(°) beer used in male adults daily. The bones were tested mechanically by a three-point bending test in a Mini Bionix (MTS) testing system. The bones from alcohol-fed rats were characterized by a reduction in bone density as well as in ash, calcium and phosphate content. In alcohol-fed rats the reduction in bone mineral density (10 %) was reflected by about 12 % reduction of mechanical strength of femur (158+/-5.5 vs. 178+/-3.2 N/mm(2)). Alcohol significantly altered femoral cortical thickness. In our experiment alcohol itself did not exert any antiandrogenic effect and it did not produce changes in the weight of seminal vesicles. Liver function test (GGT, ALP, AST) did not differ between alcohol-fed rats and control rats. Alcohol-induced bone loss is associated with increased bone resorption and decreased bone formation. These results document the efficacy of alcohol at the dose of 7.6 g 95 % ethanol/kg b.w. to cause bone loss and loss of bone mechanical strength in intact rats. The results of the present study may be interpreted as supporting the hypothesis of alcohol as a risk factor for osteoporosis.

• MeSH
• biologické markery krev   MeSH
• biomechanika MeSH
• časové faktory MeSH
• enzymy krev   MeSH
• ethanol aplikace a dávkování   toxicita   MeSH
• femur účinky léků   metabolismus   patologie   MeSH
• fosfáty krev   MeSH
• jaterní testy MeSH
• játra účinky léků   enzymologie   MeSH
• kostní denzita účinky léků   MeSH
• krysa rodu Rattus MeSH
• osteogeneze účinky léků   MeSH
• osteoporóza chemicky indukované   metabolismus   patologie   MeSH
• pití alkoholu škodlivé účinky   MeSH
• potkani Wistar MeSH
• resorpce kosti chemicky indukované   metabolismus   patologie   MeSH
• semenné váčky účinky léků   MeSH
• vápník krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• enzymy MeSH
• ethanol MeSH
• fosfáty MeSH
• vápník MeSH

The aim of this study was to assess the effects of the antiresorptive treatments of alendronate (ALN), risedronate (RIS) and raloxifene (RLX) on the response of bone to endogenous parathyroid hormone (PTH) induced by acute hypocalcemia. Forty women (age, 55-80 years) with postmenopausal osteoporosis (treated with ALN, RIS and RLX or untreated-control group) were given infusions of sodium ethylenediaminetetraacetic acid (EDTA; 10 mg/kg of body weight). Serum ionized calcium (iCa), plasma intact PTH and marker of bone resorption, serum beta C-terminal telopeptide of type I collagen (beta-CTX; beta CrossLaps) were followed for 180 min. In all women, decrease in serum iCa following the EDTA load resulted in an acute increase in serum PTH. Between 60 and 180 min, plasma PTH in the ALN and RIS treated women remained significantly higher than in the control group. The integrated beta-CTX responses (area under curves, AUCs) to peaks of PTH were significantly lower in the ALN treated women than in those treated with RIS, RLX or control group. There was no significant difference in beta-CTX AUC response to PTH between RIS, RLX and control women. Taken together, these findings suggest that in women with postmenopausal osteoporosis treated with ALN, a substantial reduction of bone turnover blunts the acute bone resorbing effect of endogenous PTH.

• MeSH
• alendronát terapeutické užití   MeSH
• biologické markery krev   MeSH
• chelátory farmakologie   MeSH
• EDTA farmakologie   MeSH
• hypokalcemie chemicky indukované   MeSH
• inhibitory kostní resorpce terapeutické užití   MeSH
• kolagen typu I účinky léků   MeSH
• kyselina etidronová analogy a deriváty   terapeutické užití   MeSH
• kyselina risedronová MeSH
• lidé středního věku MeSH
• lidé MeSH
• parathormon metabolismus   MeSH
• peptidy účinky léků   MeSH
• plocha pod křivkou MeSH
• postmenopauzální osteoporóza krev   farmakoterapie   MeSH
• raloxifen hydrochlorid terapeutické užití   MeSH
• remodelace kosti účinky léků   MeSH
• resorpce kosti metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH
• Názvy látek
• alendronát MeSH
• biologické markery MeSH
• chelátory MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• EDTA MeSH
• inhibitory kostní resorpce MeSH
• kolagen typu I MeSH
• kyselina etidronová MeSH
• kyselina risedronová MeSH
• parathormon MeSH
• peptidy MeSH
• raloxifen hydrochlorid MeSH

To elucidate the role of endogenous calcitonin (CT) in the regulation of bone resorption, we evaluated the acute effects of an intravenous calcium load in nine patients after total thyroidectomy (aged 29.2 +/- 8 years) compared with nine healthy subjects. After overnight fasting, intravenous infusions of elemental calcium 1.7 mg/kg body weight were given over a 10-minute period. Blood samples for measurements of serum ionized calcium (S-iCa), plasma intact CT, parathyroid hormone (PTH), and plasma type I collagen cross-linked C-terminal telopeptide (beta-CTX) were obtained 3 minutes before and at 13, 30, 60, 90, and 150 minutes after the start of the infusion. At baseline, parameters of calcium and bone metabolism were similar in both groups. A similar increase in S-iCa and decrease in plasma PTH levels were observed in both groups. However, the plasma CT increased significantly by 13 minutes (P < 0.05) and beta-CTX decreased significantly as early as 30 minutes (P < 0.05) (decrease by 36% as compared with the baseline) only in the group consisting of healthy individuals. In the thyroidectomized group, the plasma beta-CTX did not decrease significantly during the first 60 minutes (decrease by only 8% as compared with the baseline) and response to the calcium load was significantly diminished throughout the study period as compared with that of the healthy subjects (P < 0.01). In conclusion, the results indicate that the increased CT secretion is responsible for the rapid initial decrease in the bone resorption following an acute intravenous calcium load.

• MeSH
• dospělí MeSH
• intravenózní infuze MeSH
• kalcitonin krev   metabolismus   MeSH
• kolagen typu I MeSH
• kolagen krev   MeSH
• lidé MeSH
• mladiství MeSH
• osteoklasty účinky léků   metabolismus   MeSH
• parathormon krev   MeSH
• peptidy krev   MeSH
• resorpce kosti farmakoterapie   metabolismus   MeSH
• tyreoidektomie * MeSH
• vápník aplikace a dávkování   krev   farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• kalcitonin MeSH
• kolagen typu I MeSH
• kolagen MeSH
• parathormon MeSH
• peptidy MeSH
• vápník MeSH

Experimental hyperthyroidism had a negative effect on bone mineral density, but did not significantly alter mechanical properties of femur and femoral bone thickness. Estradiol at a dose used in humans for the treatment of osteoporosis decreased seminal vesicle weight and concentration of testosterone but increased bone density in male rats compared to intact animals. In these rats, the mechanical analysis revealed an increased mechanical femur strength higher than the increase in bone density and femoral cortical thickness. When hyperthyroid male rats with low bone density were treated with estradiol in spite of a low plasma testosterone, the changes in bone density resulting from hyperthyroidism were entirely prevented. Estrogens protect the male skeleton against resorbing action of T (3). Treatment with estradiol in male rats with hyperthyroidism did not increase mechanical bone strength or femoral cortical thickness as it did with estradiol administration alone. Our results suggest that exogenously administered estrogens may have therapeutic value in preventing bone loss accompanying triiodothyronine administration, even in male rats with a low testosterone levels. At the concentration studied, estradiol increased in spite of low plasma testosterone, bone mineral density, mechanical strength of femur, and femoral cortical thickness.

• MeSH
• analýza párové shody MeSH
• estradiol aplikace a dávkování   analogy a deriváty   fyziologie   MeSH
• hypertyreóza chemicky indukované   metabolismus   MeSH
• kostní denzita fyziologie   MeSH
• krysa rodu Rattus MeSH
• metabolické nemoci kostí chemicky indukované   patofyziologie   MeSH
• potkani Wistar MeSH
• resorpce kosti metabolismus   MeSH
• semenné váčky patologie   patofyziologie   MeSH
• testosteron krev   MeSH
• trijodthyronin MeSH
• velikost orgánu MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• estradiol 3-benzoate MeSH Prohlížeč
• estradiol MeSH
• testosteron MeSH
• trijodthyronin MeSH

The purpose of this investigation was to test the hypothesis that the decrease in bone resorption after the calcium (Ca) load can be assessed by serum type 1 collagen cross-linked C-telopeptide (Elecsys beta-CrossLaps, Roche) (S-CTX). Six young healthy women (23-27 years of age) and six healthy late postmenopausal women (63-69 years of age) with normal bone mineral density (BMD) received, after overnight fasting, 1 g of elemental Ca (in the form of calcium carbonate) dissolved in 250 ml of water or only plain water (fasting period). In addition, the late postmenopausal women were tested with an additional dose of 0.2 g of elemental Ca in 250 ml of water. Serum ionized Ca (S-iCa), S-CTX, plasma immunoreactive intact parathormone (P-PTH) were measured before and during the 5 hours after the oral intake of Ca. Urine was collected at regular intervals, and urinary Ca and creatinine were analyzed. In both the young and late postmenopausal subjects, the load with Ca resulted in a significant increase in S-iCa and urine Ca/creatinine ratio as well and a significant decrease of P-PTH and S-CTX compared with the fasting period. The comparison of the effects of 1 g Ca load between young and late postmenopausal women did not show any statistical significance in any measured parameters. In the late postmenopausal women, a significantly greater increase in S-iCa concentrations and a significantly greater decrease in P-PTH after 1 g were observed compared with those after a 0.2 g dose of Ca. During the first 3 hours, the load of both 1 g and 0.2 g of Ca induced a similar decrease in S-CTX. After 5 hours, however, S-CTX were significantly more suppressed after a 1 g dose than after a 0.2 g dose of Ca. In conclusion, a single oral morning dose of 1 g Ca suppresses bone resorption, as assessed by S-CTX, to a similar degree in both young and late postmenopausal women with normal Ca absorption. In healthy late postmenopausal women the load of 0.2 g of Ca carbonate significantly suppresses bone resorption.

• MeSH
• aplikace orální MeSH
• bederní obratle diagnostické zobrazování   metabolismus   MeSH
• biologické markery krev   MeSH
• cirkadiánní rytmus MeSH
• dospělí MeSH
• kolagen typu I MeSH
• kolagen krev   MeSH
• kostní denzita MeSH
• krček femuru diagnostické zobrazování   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• parathormon krev   MeSH
• peptidy krev   MeSH
• postmenopauza MeSH
• rentgendiagnostika MeSH
• resorpce kosti metabolismus   MeSH
• senioři MeSH
• vápník aplikace a dávkování   analýza   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• collagen type I trimeric cross-linked peptide MeSH Prohlížeč
• kolagen typu I MeSH
• kolagen MeSH
• parathormon MeSH
• peptidy MeSH
• vápník MeSH

So far it is not known whether the growth hormone (GH) has an effect on the local blood circulation in bones. Using male rats we studied the local blood circulation in the tibia and the distal end of the femur (by means of the uptake of 85Sr-microspheres), the density and ash weight of the tibia, the urinary excretion of pyridinoline (PD) and deoxypyridinoline (DPD) as an indicator of bone resorption and the blood levels of IGF-I after the administration of human GH (4 mg/kg s.c. daily for 4 weeks) and/or bisphosphonate pamidronate (Aredia, CIBA-Geigy, administered in the dose of 3 mg/kg i.p. on day 1, 2, 9 and 10). The rats were divided into four groups: 1. controls, 2. GH, 3. pamidronate, 4. GH plus pamidronate. After the administration of GH, we observed a significant increase in bone blood flow (and in the uptake of 85Sr-microspheres), a decrease in the density and ash weight of the tibia and increased urinary excretion of PD and DPD; IGF-I levels in the blood were non-significantly elevated. Simultaneously administered pamidronate inhibited all significant effects of GH and it also decreased the IGF-I levels in rats treated with GH. After the administration of pamidronate itself the bone density and ash weight of the tibia were increased and urinary DPD excretion was decreased. In view of the known vascular effects of IGF-I, we assume that the increase in bone blood flow after the administration of GH and its reduction after simultaneous administration of pamidronate could be mediated by the changes of IGF-I blood levels, although the effect of pamidronate on IGF-I is still not clear. Regarding the role of blood circulation in rat bones, we consider that our present results are further evidence for the relationship between the blood circulation in bones and bone resorption, although these results do not show how active is bone blood circulation in the regulation of bone tissue metabolism.

• MeSH
• aminokyseliny moč   MeSH
• bisfosfonáty farmakologie   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kosti a kostní tkáň krevní zásobení   účinky léků   metabolismus   MeSH
• kostní denzita účinky léků   MeSH
• krysa rodu Rattus MeSH
• mikrosféry MeSH
• minutový srdeční výdej účinky léků   MeSH
• pamidronát MeSH
• resorpce kosti chemicky indukované   metabolismus   MeSH
• růstový hormon farmakologie   MeSH
• tělesná hmotnost účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aminokyseliny MeSH
• bisfosfonáty MeSH
• deoxypyridinoline MeSH Prohlížeč
• insulinu podobný růstový faktor I MeSH
• pamidronát MeSH
• pyridinoline MeSH Prohlížeč
• růstový hormon MeSH

Transient hyperphosphatasaemia (TH) is a benign disorder characterized by transient elevation of S-ALP activity not exceeding duration of 4 months in children under 5 years of age, with elevated activity of bone isoenzymes of ALP with no signs of bone or liver disease and variable unrelated symptoms. We observed 19 children with TH and in 3 patients with markedly elevated S-ALP activity we found increased excretion of urinary hydroxyproline, suggesting increased bone resorption followed by bone formation. In 3 children with history of TH, bone mineral density (BMD) was measured and found to be normal. Transient increased bone resorption followed by bone formation during the course of TH can not be ruled out, but this has no negative impact on BMD.

• MeSH
• alkalická fosfatasa krev   MeSH
• hydroxyprolin moč   MeSH
• izoenzymy krev   MeSH
• kojenec MeSH
• kosti a kostní tkáň metabolismus   MeSH
• kostní denzita MeSH
• lidé MeSH
• minerály metabolismus   MeSH
• předškolní dítě MeSH
• resorpce kosti metabolismus   MeSH
• Check Tag
• kojenec MeSH
• lidé MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alkalická fosfatasa MeSH
• hydroxyprolin MeSH
• izoenzymy MeSH
• minerály MeSH

Plasma tartrate-resistant acid phosphatase (TR ACP), urinary hydroxyproline excretion (UH), serum osteocalcin, and bone alkaline phosphatase isozyme were determined in a prospective study in 31 women who had undergone bilateral ovariectomy (OOX). Nine patients were followed up for 1 year without treatment and for the following 3 years when on mestranol (M) substitution. On the basis of UH, 22 patients were identified as having increased bone resorption (BR) within 3 months of OOX. Subsequently, 11 patients were treated with transdermal estradiol (E2) and 11 patients with norethisterone (norethindrone, NE). In untreated patients, the biochemical indices of BR peaked 3-6 months following OOX and biochemical indices of bone formation (BF) continued to increase from 3 until 12 months. The substitution with both E2 or M resulted in normalization in serum and urinary calcium, serum phosphate, renal threshold phosphate concentration (TmPO4/GRF), and biochemical indices of BR within 4 months of treatment. Biochemical indices of BF normalized within 6 months of treatment. In the M-treated group, these effects continued for 3 years of the follow-up. The hormonal substitution had a protective effect on cortical and lumbar spine bone mass. A significant decrease, but not to normal values, in biochemical indices of BR and a persistent elevation in indices of BF were found in NE-treated patients. Unlike E2, NE does not depress osteoblastic function. There is strong evidence supporting the utility of measurements of TR ACP in plasma in examination of women who had ovariectomies and in assessement of the efficacy of treatment.

• MeSH
• dospělí MeSH
• estrogeny terapeutické užití   MeSH
• kyselá fosfatasa krev   MeSH
• léková rezistence fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• menopauza metabolismus   fyziologie   MeSH
• norethindron terapeutické užití   MeSH
• ovarektomie MeSH
• resorpce kosti farmakoterapie   metabolismus   patofyziologie   MeSH
• tartaráty farmakologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• estrogeny MeSH
• kyselá fosfatasa MeSH
• norethindron MeSH
• tartaráty MeSH