scholarly journals Regulation and enzymatic basis of bone resorption by human osteoclasts

2007 ◽  
Vol 112 (11) ◽  
pp. 567-575 ◽  
Author(s):  
Karen Fuller ◽  
Barrie Kirstein ◽  
Timothy J. Chambers
Keyword(s):  
Bone Resorption ◽  
Type I Collagen ◽  
Control Period ◽  
Cysteine Protease Inhibitor ◽  
Type I ◽  
Small Contribution ◽  
Short Period ◽  
Osteoclastic Differentiation ◽  
Human Osteoclasts ◽  
Resorptive Activity

Although much has been learned recently of the mechanisms that regulate osteoclastic differentiation, much less is known of the means through which their resorptive activity is controlled. This is especially so for human osteoclasts. We have recently developed an assay that allows us to measure resorptive activity while minimizing confounding effects on differentiation by optimizing osteoclastogenesis, so that measurable resorption occurs over a short period, and by relating resorption in each culture during the test period to the resorption that had occurred in the same culture in a prior control period. In the present study, we found that RANKL (receptor activator of nuclear factor κB ligand) strongly stimulated the release of CTX-I (C-terminal telopeptide degradation product of type I collagen) by osteoclasts over a similar range to that over which it induces osteoclastic differentiation, consistent with a distinct action on osteoclastic function. CT (calcitonin) dose-dependently inhibited bone resorption, whereas PTH (parathyroid hormone), IL (interleukin)-1, TNF-α (tumour necrosis factor-α), IL-6, IL-8, VEGF (vascular endothelial growth factor), MCP-1 (monocyte chemoattractant protein-1), MIP-1γ (macrophage inflammatory protein-1γ), IFN (interferon)-γ and dibutyryl cGMP had no significant effect. Ca2+, cyclosporin A, IFN-β and dibutyryl cAMP all strongly suppressed resorption. Bone resorption was also strongly suppressed by alendronate, the cysteine protease inhibitor E64 and the cathepsin K inhibitor MV061194. Inhibitors of MMPs (matrix metalloproteinases) had no effect on CTX-I release. Moreover, the release of the MMP-derived collagen fragment ICTP (C-terminal cross-linked telopeptide of type I collagen) represented less that 0.01% of the quantity of CTX-I released in our cultures. This suggests that MMPs make, at most, a very small contribution to the bone-resorptive activity of osteoclasts.

scholarly journals Marker of Bone Resorption in Acute Response to Exogenous or Endogenous Parathyroid Hormone

2008 ◽  
Vol 3 ◽  
pp. 117727190800300 ◽  
Author(s):  
Vit Zikan ◽  
Jan J. Stepan
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Type I Collagen ◽  
Control Period ◽  
Bone Resorption Marker ◽  
Type I ◽  
Healthy Men ◽  
Acute Response ◽  
Acute Increase ◽  
Edta Infusion

Parathyroid hormone (PTH) changes morphology of osteoclasts within minutes after its systemic administration. The aim of our study was to test in healthy men whether both exogenous and endogenous PTH could change acutely (minutes to hours) the serum cross-linked C-telopeptide of type I collagen (beta CTX), which is released during osteoclastic resorption of bone. Twelve healthy men (age range 24–34 yr) were each studied during 180 min on a control period, after a single subcutaneous injection of teriparatide, and after 30 min EDTA infusion to stimulate endogenous PTH secretion. The tests were started after overnight fast, 3 h after a standard calcium load. The EDTA infusion induced a significant decrease in serum ionized calcium (by 8.5% at 33 min) and a significant increase in plasma PTH (by 305% at 33 min). Both the EDTA and teriparatide resulted in a significant increase in beta CTX (p < 0.001) with maximum increases of 64% and 80%, respectively. A mild, but significant decrease in beta CTX was observed during the control test period. In conclusion, single-dose teriparatide injection as well as a stimulation of endogenous PTH in healthy men results in an acute increase of the bone resorption marker.

Different responses of biochemical markers of bone resorption to bisphosphonate therapy in Paget disease

1995 ◽  
Vol 41 (11) ◽  
pp. 1592-1598 ◽  
Author(s):  
A Blumsohn ◽  
K E Naylor ◽  
A M Assiri ◽  
R Eastell
Keyword(s):  
Bone Resorption ◽  
Biochemical Markers ◽  
Type I Collagen ◽  
Bisphosphonate Therapy ◽  
Response To Therapy ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Paget Disease ◽  
Markers Of Bone Resorption ◽  
Total Alkaline

Abstract We examined the response of different biochemical markers of bone resorption to bisphosphonate therapy (400 mg of etidronate daily for 6 months) in mild Paget disease (n = 14). Urinary markers included hydroxyproline (OHP), total (T) and free (F) pyridinolines (Pyds) determined by HPLC, immunoreactive FPyds, immunoreactive TPyds, and the N- and C-terminal telopeptides of type I collage (NTx, CL). Serum measurements included tartrate-resistant acid phosphatase (TRAcP) and the C-terminal telopeptide of type I collagen (ICTP). ICTP and TRAcP showed a minimal response to therapy (% change at 6 months, -13.1 +/- 6.8 and -6.7 +/- 3.4, respectively). The response was greatest for urinary telopeptides (NTx and CL; % change -75.7 +/- 7.5 and -73.4 +/- 8.9, respectively). The response was somewhat greater for TPyds than for FPyds. We conclude that: (a) ICTP and TRAcP are unreliable indicators of changes in bone turnover; (b) oligopeptide-bound Pyds and telopeptide fragments of type I collagen in urine show a somewhat greater response to therapy than do FPyds and may be more sensitive indicators of bone resorption; and (c) as yet no evidence suggests that these markers are substantially better predictors of the clinical response to therapy than serum total alkaline phosphatase or urinary OHP. There are several problems with the interpretation of these measurements in Paget disease, and the clinical utility of these measurements remains uncertain.

Carboxyterminal telopeptide of type I collagen, ICTP, as a marker of matrix degradation in neonatal mouse calvarial bones, in vitro

1992 ◽  
Vol 12 (5) ◽  
pp. 407-411 ◽  
Author(s):  
Östen Ljunggren ◽  
Sverker Ljunghall
Keyword(s):  
Parathyroid Hormone ◽  
Bone Resorption ◽  
Type I Collagen ◽  
Bone Matrix ◽  
Neonatal Mouse ◽  
Type I ◽  
Matrix Degradation ◽  
Dose Responses ◽  
Carboxyterminal Telopeptide

Bone resorption, in vitro, is often measured as the release of prelabelled45Ca from neonatal mouse calvarial bones, or from fetal rat long bones. In this report we describe a technique to measure the breakdown of bone-matrix, in vitro. We also describe a new way to dissect neonatal mouse calvarial bones, in order to obtain large amounts of bone samples. Twelve bone fragments were dissected out from each mouse calvaria and were thereafter cultured in CMRL 1066 culture medium in serum-free conditions in 0.5 cm2 multiwell culture dishes. Matrix degradation after treatment with parathyroid hormone was assessed by measuring the amount of carboxyterminal telopeptide of type I collagen (ICTP) by RIA. The data on matrix degradation was compared to the release of prelabelled45Ca from neonatal mouse calvarial bones. We found that the dose-responses for parathyroid hormone-induced release of prelabelled45Ca and ICTP were identical. In conclusion: RIA-analysis of the ICTP-release is an easy and accurate method to measure degradation of bone-matrix, in vitro. Furthermore, the new dissection technique, described in this report, makes it easy to obtain large amounts of bone samples and thus to perform extensive experiments, e.g. dose-responses for agents that enhance bone resorption.

scholarly journals Oligogalacturonic acid inhibit bone resorption and collagen degradation through its interaction with type I collagen

2009 ◽  
Vol 78 (12) ◽  
pp. 1448-1455 ◽  
Author(s):  
Jean-Marc Lion ◽  
Romuald Mentaverri ◽  
Stéphanie Rossard ◽  
Nathalie Jullian ◽  
Bernard Courtois ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Type I Collagen ◽  
Collagen Degradation ◽  
Type I ◽  
Inhibit Bone Resorption ◽  
Oligogalacturonic Acid

scholarly journals Coated-tube radioimmunoassay for C-telopeptides of type I collagen to assess bone resorption

1996 ◽  
Vol 42 (10) ◽  
pp. 1639-1644 ◽  
Author(s):  
M Bonde ◽  
C Fledelius ◽  
P Qvist ◽  
C Christiansen
Keyword(s):  
Bone Resorption ◽  
Postmenopausal Women ◽  
Type I Collagen ◽  
Premenopausal Women ◽  
Type I ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Analytical Recovery ◽  
Controlled Clinical Study ◽  
Different Doses

Abstract We present a coated-tube RIA that is useful for assessment of bone resorption. The assay uses a monoclonal antibody raised against a linear 8-amino-acid sequence (EKAHDGGR) derived from the C-telopeptides of type I collagen. Within-run and total CVs were 4.4% and 5.3-6.2%, respectively, at concentrations of 1-7 mg/L (n = 4-20). Analytical recovery was 98% +/- 8% and dilution 97% +/- 7%. Values obtained in a group of 36 premenopausal women were 227 +/- 89.6 mg/mol creatinine. In a group of 141 postmenopausal women, the values obtained were 429 +/- 225 mg/mol creatinine, a highly significant increase of 89% (P &lt;0.001) over the premenopausal value. In a double-blind placebo-controlled clinical study of these postmenopausal women receiving five different doses of a bisphosphonate, a significant decrease of RIA-measured C-telopeptide values was seen in all bisphosphonate-treated groups, after just 3 months. Values in urine samples from postmenopausal women assayed with the RIA (gamma) and the CrossLaps(TM) ELISA (x) agreed well: slope = 0.98 (95% confidence interval, 0.94-1.01), intercept = 0.34 (0.25-0.43) mg/L, and Sylx = 0.93 mg/L (n = 678). We conclude that this RIA represents a valuable tool for assessing bone resorption.

scholarly journals Space Flight Is Associated with Rapid Decreases of Undercarboxylated Osteocalcin and Increases of Markers of Bone Resorption without Changes in Their Circadian Variation: Observations in Two Cosmonauts

2000 ◽  
Vol 46 (8) ◽  
pp. 1136-1143 ◽  
Author(s):  
Anne Caillot-Augusseau ◽  
Laurence Vico ◽  
Martina Heer ◽  
Dimitri Voroviev ◽  
Jean-Claude Souberbielle ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Remodeling ◽  
Vitamin K ◽  
Space Flight ◽  
Type I Collagen ◽  
Circadian Variation ◽  
Bone Alkaline Phosphatase ◽  
Type I ◽  
Undercarboxylated Osteocalcin ◽  
Type I Procollagen

Abstract Background: Microgravity induces bone loss by mechanism(s) that remain largely unknown. Methods: We measured biochemical markers related to bone remodeling in two cosmonauts before, during, and after 21- and 180-day space flights, respectively. Results: During both flights, type I procollagen propeptide and bone alkaline phosphatase decreased as early as 8 days after launch. Undercarboxylated osteocalcin percentage increased early and remained high during both flights. Vitamin K supplementation restored carboxylation of osteocalcin during the long-term flight. Urinary and serum C-telopeptide of type I collagen (CTX) increased as early as day 8 of the flights; the increase was greater in serum than in urine. Pyridinoline, free deoxypyridinoline, and N-telopeptide increased less than CTX during the short-term space flight. The circadian rhythm of bone resorption assessed by urine CTX and free deoxypyridinoline was not altered by microgravity. Conclusion: Vitamin K metabolism or action and bone remodeling may be altered in cosmonauts.

Cysteine proteinase activities in the fish pathogenPhilasterides dicentrarchi(Ciliophora: Scuticociliatida)

Parasitology ◽  
2004 ◽  
Vol 128 (5) ◽  
pp. 541-548 ◽  
Author(s):  
A. PARAMÁ ◽  
R. IGLESIAS ◽  
M. F. ÁLVAREZ ◽  
J. LEIRO ◽  
F. M. UBEIRA ◽  
...  
Keyword(s):  
Crude Extract ◽  
Type I Collagen ◽  
Cysteine Proteinase ◽  
Cysteine Proteases ◽  
Cysteine Protease Inhibitor ◽  
Type I ◽  
Molecular Weights ◽  
Reducing Conditions ◽  
Sds Page

This study investigated protease activities in a crude extract andin vitroexcretion/secretion (E/S) products ofPhilasterides dicentrarchi, a ciliate fish parasite causing economically significant losses in aquaculture. Gelatin/SDS–PAGE analysis (pH 4, reducing conditions) detected 7 bands with gelatinolytic activity (approximate molecular weights 30–63 kDa) in the crude extract. The banding pattern observed in analysis of E/S products was practically identical, except for 1 low-molecular-weight band detected in the crude extract but not in the E/S products. In assays with synthetic peptidep-nitroanilide substrates, the crude extract hydrolysed substrates characteristic of cysteine proteases, namely Z-Arg-Arg pNA, Bz-Phe-Val-Arg pNA and Z-Phe-Arg pNA. These activities were strongly inhibited by the cysteine protease inhibitor E-64 and by Ac-Leu-Val-Lys aldehyde, a potent inhibitor of cysteine proteases of the cathepsin B protease subfamily. The proteases present in the crude extract degraded both type-I collagen and haemoglobinin vitro, consistent with roles in tissue invasion and nutrition respectively. Again, E-64 completely (collagen) or markedly (haemoglobin) inhibited this degradation. Finally, the histolytic activity of the ciliate in turbot fibroblast monolayers was strongly reduced in the presence of E-64, confirming the importance of secreted cysteine proteinases in the biology ofPhilasterides dicentrarchi.

Effects of transdermal estrogen on collagen turnover at rest and in response to exercise in postmenopausal women

2012 ◽  
Vol 113 (7) ◽  
pp. 1040-1047 ◽  
Author(s):  
J. Pingel ◽  
H. Langberg ◽  
D. Skovgård ◽  
S. Koskinen ◽  
A. Flyvbjerg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Postmenopausal Women ◽  
Acute Exercise ◽  
Type I Collagen ◽  
Control Period ◽  
Vastus Lateralis Muscle ◽  
Type I ◽  
Relative Role ◽  
Igf I ◽  
Transdermal Estrogen

Menopause is associated with loss of collagen content in the skin and tendon as well as accumulation of noncontractile tissue in skeletal muscle. The relative role of hormones and physical activity on these changes is not known. Accordingly, in a randomized, controlled, crossover study we investigated effects of transdermal estrogen replacement therapy (ERT) on type I collagen synthesis in tendon and skeletal muscle in 11 postmenopausal women. Patches with estrogen (Evorel) were placed on the skin above the patellar tendons and compared with no patch (control period). On day 2 all subjects performed one-legged exercise, and thereafter the exercised leg (EX leg) was compared with the nonexercised leg (Rest leg). Microdialysis catheters were placed in front of the patellar tendons and in the vastus lateralis muscle of both legs at days 3 and 5. The collected dialysate was analyzed for procollagen type I NH2-terminal propeptide (PINP), insulin-like growth factor I (IGF-I), and interleukin-6 (IL-6). Neither loading (Rest leg vs. EX leg) nor treatment (control vs. ERT) influenced peritendinous PINP, whereas combined exercise and ERT enhanced muscle PINP after 72 h (interaction between loading and treatment P = 0.008). In neither skeletal muscle nor peritendinous fluid were IGF-I and IL-6 influenced by treatment or exercise. In conclusion, ERT was associated with enhanced synthesis of type I collagen in the skeletal muscle in response to acute exercise. In perspective, this indicates that the availability of estrogen in postmenopausal women is important for repair of muscle damage or remodeling of the connective tissue within the skeletal muscle after exercise.

Markers of Bone Formation and Resorption Identify Subgroups of Patients with Clinical Knee Osteoarthritis Who Have Reduced Rates of Cartilage Loss

2010 ◽  
Vol 37 (6) ◽  
pp. 1252-1259 ◽  
Author(s):  
PATRICIA A. BERRY ◽  
ROSE A. MACIEWICZ ◽  
FLAVIA M. CICUTTINI ◽  
MARK D. JONES ◽  
CAROLINE J. HELLAWELL ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Formation ◽  
Type I Collagen ◽  
Serum Markers ◽  
Cartilage Volume ◽  
Cartilage Loss ◽  
Type I ◽  
Bone Formation Markers ◽  
Markers Of Bone Formation ◽  
Markers Of Bone Resorption

Objective.To determine whether serum markers of bone formation and resorption, used individually or in combination, can be used to identify subgroups who lose cartilage volume at different rates over 2 years within a knee osteoarthritis (OA) population.Methods.Changes in cartilage volume over 2 years were measured in 117 subjects with knee OA using magnetic resonance imaging. We examined relationships between change in cartilage volume and baseline serum markers of bone formation [intact N-terminal propeptide of type I procollagen (PINP) and osteocalcin] and resorption [N-telopeptide of type I collagen (NTX-I), C-telopeptide of type I collagen (CTX-I), and C-telopeptide of type I collagen (ICTP).Results.The baseline markers of bone formation, PINP and osteocalcin (p = 0.02, p = 0.01, respectively), and the baseline markers of bone resorption, CTX-I and NTX-I (p = 0.02 for both), were significantly associated with reduced cartilage loss. There were no significant associations between baseline ratios of bone formation to resorption markers and cartilage loss. However, when subjects were divided into subgroups with high or low bone formation markers (based on levels of marker ≥ mean or < mean for the population, respectively), in the subgroup with high PINP there was a significant association between increasing bone resorption markers CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.001, respectively). Similarly, in the subgroup with high osteocalcin, there was a significant association between increasing CTX-I and NTX-I and reduced cartilage loss (p = 0.02, p = 0.003, respectively). In contrast, in subgroups with low bone formation markers, no significant associations were obtained between markers of bone resorption and cartilage loss.Conclusion.Overall, the results suggest that higher bone remodeling (i.e., higher serum levels of bone formation and resorption) is associated with reduced cartilage loss. Considering markers of bone formation and resorption together, it is possible to identify subgroups within the OA population who have reduced rates of cartilage loss.

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