The bone formation marker N-terminal propeptide of type I collagen is also a marker for fibrogenesis in aged bile duct ligated rats

Abstract Purpose/introduction To compare serum levels of bone turnover markers in athletes and non-athletes, and to evaluate the relationship between serum levels of vitamin D metabolites and exercise-induced changes in biomarker levels. Methods Sixteen elite male artistic gymnasts (EG; 21.4 ± 0.8 years-old) and 16 physically active men (the control group, PAM; 20.9 ± 1.2 years-old) performed lower and upper body 30-s Wingate anaerobic tests (LBWT and UBWT, respectively). For biomarker analysis, blood samples were collected before, and 5 and 30 min after exercise. Samples for vitamin D levels were collected before exercise. N-terminal propeptide of type I collagen (PINP) was analysed as a marker of bone formation. C-terminal telopeptide of type I collagen (CTX) was analysed as a marker of bone resorption. Results UBWT fitness readings were better in the EG group than in the PAM group, with no difference in LBWT readings between the groups. UBWT mean power was 8.8% higher in subjects with 25(OH)D3 levels over 22.50 ng/ml and in those with 24,25(OH)2D3 levels over 1.27 ng/ml. Serum CTX levels increased after both tests in the PAM group, with no change in the EG group. PINP levels did not change in either group; however, in PAM subjects with 25(OH)D3 levels above the median, they were higher than those in EG subjects. Conclusion Vitamin D metabolites affect the anaerobic performance and bone turnover markers at rest and after exercise. Further, adaptation to physical activity modulates the effect of anaerobic exercise on bone metabolism markers.

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Trabecular Bone is Increased in a Rat Model of Polycystic Ovary Syndrome

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1284-5491 ◽

2020 ◽

Author(s):

Lady Katerine Serrano Mujica ◽

Werner Giehl Glanzner ◽

Amanda Luiza Prante ◽

Vitor Braga Rissi ◽

Gabrielle Rebeca Everling Correa ◽

...

Keyword(s):

Polycystic Ovary Syndrome ◽

Bone Formation ◽

Type I Collagen ◽

Polycystic Ovary ◽

Osteoclast Differentiation ◽

Bone Volume ◽

Negative Regulator ◽

Type I ◽

Ovary Syndrome ◽

The Impact

AbstractPolycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

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Tissue Engineering of Bone by Osteoinductive Biomaterials

MRS Bulletin ◽

10.1557/s0883769400031833 ◽

1996 ◽

Vol 21 (11) ◽

pp. 36-39 ◽

Cited By ~ 40

Author(s):

Ugo Ripamonti ◽

Nicolaas Duneas

Keyword(s):

Tissue Engineering ◽

Bone Formation ◽

Type I Collagen ◽

Demineralized Bone Matrix ◽

Bone Matrix ◽

Mesenchymal Cells ◽

Tissue Response ◽

Type I ◽

New Bone Formation ◽

Demineralized Bone

Recent advances in materials science and biotechnology have given birth to the new and exciting field of tissue engineering, in which the two normally disparate fields are merging into a profitable matrimony. In particular the use of biomaterials capable of initiating new bone formation via a process called osteoinduction is leading to quantum leaps for the tissue engineering of bone.The classic work of Marshall R. Urist and A. Hari Reddi opened the field of osteoinductive biomaterials. Urist discovered that, upon implantation of devitalized, demineralized bone matrix in the muscle of experimental animals, new bone formation occurs within two weeks, a phenomenon he described as bone formation by induction. The tissue response elicited by implantation of demineralized bone matrix in muscle or under the skin includes activation and migration of undifferentiated mesenchymal cells by chemotaxis, anchoragedependent cell attachment to the matrix, mitosis and proliferation of mesenchymal cells, differentiation of cartilage, mineralization of the cartilage, vascular invasion of the cartilage, differentiation of osteoblasts and deposition of bone matrix, and finally mineralization of bone and differentiation of marrow in the newly developed ossicle.The osteoinductive ability of the extracellular matrix of bone is abolished by the dissociative extraction of the demineralized matrix, but is recovered when the extracted component, itself inactive, is reconstituted with the inactive residue—mainly insoluble collagenous bone matrix. This important experiment showed that the osteoinductive signal resides in the solubilized component but needs to be reconstituted with an appropriate carrier to restore the osteoinductive activity. In this case, the carrier is the insoluble collagenous bone matrix—mainly crosslinked type I collagen.

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Vitamin K promotes mineralization, osteoblast-to-osteocyte transition, and an anticatabolic phenotype by γ-carboxylation-dependent and -independent mechanisms

AJP Cell Physiology ◽

10.1152/ajpcell.00216.2009 ◽

2009 ◽

Vol 297 (6) ◽

pp. C1358-C1367 ◽

Cited By ~ 62

Author(s):

Gerald J. Atkins ◽

Katie J. Welldon ◽

Asiri R. Wijenayaka ◽

Lynda F. Bonewald ◽

David M. Findlay

Keyword(s):

Bone Formation ◽

Vitamin K ◽

Type I Collagen ◽

Vitamin K2 ◽

Type I ◽

Vitamin K1 ◽

Vitamin K3 ◽

Positive Effect

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.

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Reduced Serum Levels of Bone Formation Marker P1NP in Psoriasis

Frontiers in Medicine ◽

10.3389/fmed.2021.730164 ◽

2021 ◽

Vol 8 ◽

Author(s):

Julia Mentzel ◽

Tabea Kynast ◽

Johannes Kohlmann ◽

Holger Kirsten ◽

Matthias Blüher ◽

...

Keyword(s):

Bone Formation ◽

Bone Metabolism ◽

Type I Collagen ◽

Skin Inflammation ◽

Serum Levels ◽

Serum Markers ◽

Chronic Inflammatory Disease ◽

Type I ◽

Patient Counseling ◽

Type I Procollagen

Psoriasis is a chronic inflammatory disease of the skin and joints. More recent data emphasize an association with dysregulated glucose and fatty acid metabolism, obesity, elevated blood pressure and cardiac disease, summarized as metabolic syndrome. TNF-α and IL-17, central players in the pathogenesis of psoriasis, are known to impair bone formation. Therefore, the relation between psoriasis and bone metabolism parameters was investigated. Two serum markers of either bone formation—N-terminal propeptide of type I procollagen (P1NP) or bone resorption—C-terminal telopeptide of type I collagen (CTX-I)—were analyzed in a cohort of patients with psoriasis vulgaris. In patients with psoriasis, P1NP serum levels were reduced compared to gender-, age-, and body mass index-matched healthy controls. CTX-I levels were indistinguishable between patients with psoriasis and controls. Consistently, induction of psoriasis-like skin inflammation in mice decreases bone volume and activity of osteoblasts. Moreover, efficient anti-psoriatic treatment improved psoriasis severity, but did not reverse decreased P1NP level suggesting that independent of efficient skin treatment psoriasis did affect bone metabolism and might favor the development of osteoporosis. Taken together, evidence is provided that bone metabolism might be affected by psoriatic inflammation, which may have consequences for future patient counseling and disease monitoring.

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The Effect of the Combination of Vitamin K2 and Genistein, Coumestrol and Daidzein on the Osteoblast Differentiation and Bone Matrix Formation

Journal of Biotechnology Research Center ◽

10.24126/jobrc.2016.10.2.474 ◽

2016 ◽

Vol 10 (2) ◽

pp. 12-19

Author(s):

Sahar S. Karieb ◽

Mohammed M. Jawad ◽

Hanady S. Al-Shmgani ◽

Zahraa H.M. Kadri

Keyword(s):

Bone Formation ◽

Osteoblast Differentiation ◽

Nuclear Factor Kappa B ◽

Type I Collagen ◽

Bone Mineralization ◽

Bone Matrix ◽

Vitamin K2 ◽

Type I ◽

Nuclear Factor ◽

Effective Factor

Multiple studies have been reported the stimulatory effect of the combinations of nutrients factors on bone formation. One such factor is vitamin K2 which can be associated with bone protective activities. The effect of vitamin K2 alone and in combination with genistein, coumestrol and daidzein on osteoblast differentiation and mineralization were tested. Significantly, vitamin K2 increased bone mineralization in combination with genistein (10-5M), coumestrol (10-7M) and daidzein (10-5M). However, there is no additive effect of this vitamin on alkaline phosphatase (ALP) levels in osteoblasts. By contrast, vitamin K2 enhanced the stimulatory effect of type I collagen and osteocalcin expression. Vitamin K2 alone increased RUNX and OSX expression while there is no synergistic effect with tested compound; this vitamin also did not modulate nuclear factor kappa B ligand (RANKL)/ osteoprotegerin (OPG) ratio expression. These results suggested that vitamin K2 can be more effective factor in the presence of phytoestrogens on the improvement of bone formation after menopause.

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288 Dietary calcium decreases digestibility of phosphorus in late gestating sows, but blood biomarkers may be used to predict bone formation and resorption

Journal of Animal Science ◽

10.1093/jas/skaa054.179 ◽

2020 ◽

Vol 98 (Supplement_3) ◽

pp. 105-106

Author(s):

Su A Lee ◽

Mike R Bedford ◽

Hans H Stein

Keyword(s):

Bone Formation ◽

Type I Collagen ◽

Linear Increase ◽

Type I ◽

Serum Concentrations ◽

Blood Biomarkers ◽

Specific Alkaline Phosphatase ◽

Bone Specific Alkaline Phosphatase ◽

P Concentration ◽

P Retention

Abstract The objective was to test the hypothesis that Ca levels in diets fed to late gestating sows affect apparent total tract digestibility (ATTD) and retention of Ca and P, blood Ca and P, and serum concentrations of hormones and blood biomarkers. Thirty-six sows (parity = 2.8) were divided in 3 blocks, housed individually in metabolism crates from d 91 to 105 of gestation and randomly allotted to 4 experimental diets containing 25, 50, 75, or 100% of the requirement for Ca with a constant P concentration. Fecal and urine samples were collected for 4 d after 5 d of adaptation. At the conclusion of the experiment, a blood sample from all sows was collected. The statistical model included diet as fixed effect and parity, block, and replicate within block as random effects. Values for the ATTD and retention of Ca increased quadratically (P < 0.05) as dietary Ca increased. Fecal P output increased linearly (P < 0.001) as dietary Ca increased, which resulted in a linear decrease (P < 0.001) in the ATTD of P. Urine P output decreased linearly (P < 0.001) as dietary Ca increased with a linear increase (P < 0.05) in P retention. Serum Ca and P and estrogen, calcitonin, and parathyroid hormone were not affected by dietary Ca. Carboxyterminal cross-linked telopeptide of type I collagen (CTX-I) in serum decreased linearly (P = 0.033) and bone-specific alkaline phosphatase tended to decrease linearly (P = 0.091) as Ca in diets increased. Osteocalcin in serum was not affected by Ca levels, but the ratio between osteocalcin and CTX-I tended to increase (P = 0.055) as dietary Ca increased. In conclusion, P digestibility decreases, but retention of P increases, as dietary Ca increases and blood biomarkers may be useful to predict bone formation and resorption by late gestating sows.

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Sex- and Age-Specific Reference Curves for Serum Markers of Bone Turnover in Healthy Children from 2 Months to 18 Years

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1706 ◽

2006 ◽

Vol 92 (2) ◽

pp. 443-449 ◽

Cited By ~ 160

Author(s):

Markus Rauchenzauner ◽

Andrea Schmid ◽

Peter Heinz-Erian ◽

Klaus Kapelari ◽

Gerda Falkensammer ◽

...

Keyword(s):

Bone Formation ◽

Type I Collagen ◽

Bone Markers ◽

Collagen Degradation ◽

Specific Reference ◽

Type I ◽

Healthy Children ◽

Pubertal Stage ◽

Reference Curves ◽

Carboxyterminal Telopeptide

Abstract Introduction: This study aimed to establish sex- and age-specific reference curves enabling the calculation of z-scores and to examine correlations between bone markers and anthropometric data. Methods: Morning blood samples were obtained from 572 healthy children and adolescents (300 boys) aged 2 months to 18 yr. Height, weight, and pubertal stage were recorded. Serum osteocalcin (OC), bone-specific alkaline phosphatase (BALP), type-1 collagen degradation markers [carboxyterminal telopeptide region of type I collagen (ICTP), carboxyterminal telopeptide α1 chain of type I collagen (CTX)], and tartrate-resistant acid phosphatase (TRAP5b) were measured. Cross-sectional centile charts were created for the 3rd, 50th, and 97th centiles. Results: Apart from TRAP5b, all bone markers were nonnormally distributed, requiring logarithmic (BALP, OC, ICTP) or square root (CTX) transformation. Back-transformed centile curves for age and sex are presented for practical use. All bone markers varied with age and pubertal stage (P < 0.001). Significant correlations were found between sd score (SDS) for bone formation markers BALP and OC (r = 0.13; P = 0.004), SDS for collagen degradation markers ICTP and CTX (r = 0.14; P = 0.002), and SDS for the phosphatases (r = 0.34, P < 0.001). Height and weight SDS correlated weakly with some bone marker SDS, particularly with lnBALP SDS (r = 0.20 and 0.24, respectively; both P < 0.001). Conclusion: This study provides reference curves for OC, BALP, CTX, ICTP, and TRAP5b in healthy children. Taller and heavier individuals for age had greater bone marker concentrations, likely reflecting greater growth velocity. SDS for markers of bone formation, collagen degradation, and phosphatases were each independently correlated, suggesting they derive from the same biological processes. The possibility of calculating SDS will facilitate monitoring of antiresorptive therapy or disease progression in children with metabolic bone disease.

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

The Journal of Rheumatology ◽

10.3899/jrheum.091055 ◽

2010 ◽

Vol 37 (6) ◽

pp. 1252-1259 ◽

Cited By ~ 23

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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Cytoplasmic polyadenylation by TENT5A is required for proper bone formation

10.1101/2020.08.18.256115 ◽

2020 ◽

Author(s):

Olga Gewartowska ◽

Goretti Aranaz Novaliches ◽

Paweł S Krawczyk ◽

Seweryn Mroczek ◽

Monika Kusio-Kobiałka ◽

...

Keyword(s):

Bone Formation ◽

Type I Collagen ◽

Bone Mineralization ◽

Bone Fragility ◽

Type I ◽

Human Genetic Disease ◽

Cytoplasmic Polyadenylation ◽

Disease Symptoms ◽

Biologically Relevant ◽

First Time

AbstractOsteoblasts orchestrate bone formation by secreting dense, highly cross-linked type I collagen and other proteins involved in osteogenesis. Mutations in Col1α1, Col1α2, or collagen biogenesis factors lead to the human genetic disease, osteogenesis imperfecta (OI). Herein, we show that the TENT5A gene, whose mutation is responsible for poorly characterized type XVIII OI, encodes an active cytoplasmic poly(A) polymerase regulating osteogenesis. TENT5A is induced during osteoblast differentiation and TENT5A KO osteoblasts are defective in mineralization. The TENT5A KO mouse recapitulates OI disease symptoms such as bone fragility and hypomineralization. Direct RNA sequencing revealed that TENT5A polyadenylates and increases expression of Col1α1 and Col1α2 RNAs, as well as those of other genes mutated in OI, resulting in lower production and improper folding of collagen chains. Thus, we have identified the specific pathomechanism of XVIII OI and report for the first time a biologically relevant post-transcriptional regulator of collagen production. We further postulate that TENT5A, possibly together with its paralogue TENT5C, is responsible for the wave of cytoplasmic polyadenylation of mRNAs encoding secreted proteins occurring during bone mineralization.

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