New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease.

Price, Paul A.; Parthemore, Jacqueline G.; Deftos, Leonard J.

doi:10.1172/jci109954

Cited by 637 publications

(144 citation statements)

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“…2 B). Consistent with these histological observations, circulating levels of osteocalcin, a marker of bone formation (Price et al, 1980), were decreased in 1(I) miR-34c transgenic mice, whereas those of C-terminal telopeptide of type I collagen (Ctx), a marker of bone resorption (Eyre et al, 1988), were unaffected (Figs. 2 C and S2).…”

Section: Identification Of Mirnas Differentially Expressed During Ostsupporting

confidence: 57%

miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

Yu¹,

Zheng²,

Zeng³

et al. 2012

J Exp Med

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Section: Identification Of Mirnas Differentially Expressed During Ostsupporting

confidence: 57%

miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

Yu¹,

Zheng²,

Zeng³

et al. 2012

J Exp Med

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“…Since the discovery of osteocalcin in the late 1970s (13,37,38), it has been used as a specific marker of osteoblast activity both in vivo (17,39,40) and in vitro (1,41) because of the restricted expression in the mature cells of osteoblastic lineage (15,42,43). Osteocalcin content in adult bone has been reported to range from 0.28 (human) to 2-2.5 (cow) mg/g of dry bone, and it represents up to 20% of noncollagenous bone matrix proteins (8,44).…”

Section: Discussionmentioning

confidence: 99%

Release of Intact and Fragmented Osteocalcin Molecules from Bone Matrix during Bone Resorption in Vitro

Ivaska

Hentunen

Vääräniemi

et al. 2004

Journal of Biological Chemistry

176

114

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Osteocalcin detected from serum samples is considered a specific marker of osteoblast activity and bone formation rate. However, osteocalcin embedded in bone matrix must also be released during bone resorption. To understand the contribution of each type of bone cell in circulating osteocalcin levels, we used immunoassays detecting different molecular forms of osteocalcin to monitor bone resorption in vitro. Osteoclasts were obtained from rat long bones and cultured on bovine bone slices using osteocalcin-depleted fetal bovine serum. In addition, human osteoclasts differentiated from peripheral blood mononuclear cells were used. Both rat and human osteoclasts released osteocalcin from bovine bone into medium. The amount of osteocalcin increased in the presence of parathyroid hormone, a stimulator of resorption, and decreased in the presence of bafilomycin A1, an inhibitor of resorption. The amount of osteocalcin in the medium correlated with a well characterized marker of bone resorption, the C-terminal telopeptide of type I collagen (r > 0.9, p < 0.0001). The heterogeneity of released osteocalcin was determined using reverse phase high performance liquid chromatography, and several molecular forms of osteocalcin, including intact molecule, were identified in the culture medium. In conclusion, osteocalcin is released from the bone matrix during bone resorption as intact molecules and fragments. In addition to the conventional use as a marker of bone formation, osteocalcin can be used as a marker of bone resorption in vitro. Furthermore, bone matrix-derived osteocalcin may contribute to circulating osteocalcin levels, suggesting that serum osteocalcin should be considered as a marker of bone turnover rather than bone formation. Osteocalcin (OC)1 is a 6-kDa noncollagenous protein produced by osteoblasts (1), osteocytes (2), and odontoblasts (3).Osteocalcin messenger RNA has also been detected in tissues other than bone, but it appears to be processed properly only in the bone microenvironment (4, 5). The structure of osteocalcin is characterized by three glutamic acid residues, which undergo a vitamin K-dependent carboxylation. The ␥-carboxyglutamic acid residues (Gla) provide osteocalcin with the ability to bind bone hydroxyapatite with a high affinity (6, 7). Osteocalcin is the second most abundant protein in the bone matrix, and it is highly conserved among all vertebrate species (8). The biological function of osteocalcin is probably related to the regulation of bone turnover and/or mineralization (9, 10).The expression of osteocalcin is a marker of late osteoblast differentiation and is induced only after the expression of other osteoblastic markers such as alkaline phosphatase and type I collagen (11,12). Newly synthesized osteocalcin is mostly (60 -90%) adsorbed to the bone hydroxyapatite via the Gla residues, but a part of it leaks into the circulation where it can be detected (13,14). Although osteoblasts synthesize only intact osteocalcin (15), osteocalcin may further undergo intracellular processing or ...

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“…The assay which has been described previously (Price et al, 1980) (O.1moll-1). After 15 min the reaction was stopped with 0.5 vol of sodium hydroxide (0.5moll-1) and the reaction product determined by reading absorbance at 405nm.…”

Section: Methodsmentioning

confidence: 99%

Biochemical prediction of response of bone metastases to treatment

Coleman

Whitaker²,

Moss³

et al. 1988

Br J Cancer

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Summary Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF).Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a > 10% rise in serum osteocalcin (BGP) Osteoblast activity was monitored by serial measurements of alkaline phosphatase bone isoenzyme (ALP-BI) and osteocalcin (BGP). Serum calcium, tartrate resistant acid phosphatase (TRP) and urinary excretion of calcium and hydroxyproline were measured to assess osteoclast activity. Serum for measurement of BGP, ALP-BI and TRP was obtained from a morning blood sample following centrifugation. The aliquot for TRP was acidified with 20 p1 of 5 M acetate buffer (pH 5) per ml of serum. All samples were frozen within 6 h and stored at -20°C. A morning spot urine sample was collected for measurement of calcium and hydroxyproline excretion after an overnight fast and stored at -20°C. Foods rich in collagen were avoided for 18 h prior to urine collection for hydroxyproline. Following pretreatment estimations measurements of serum calcium, BGP, and urinary calcium excretion were performed monthly, ALP-BI at 1, 3 and 6 months during treatment and TRP and urinary hydroxyproline excretion 3 monthly.Bone scans, with plain radiographs of abnormal areas, were performed before treatment and repeated three monthly. Standard overlapping views were taken 3-4h after injection of 500 megabecquerels of technetium99m labelled methylene diphosphonate (MDP). Symptomatic response was assessed by a questionnaire completed by the patient. Severity of pain and mobility were rated by the patient and combined with a scoring of analgesic consumption and the UICC performance status to produce an overall symptom score which was expressed as a percentage of the maximum possible score. (Details of pain and activity questionnaire available from the authors on request).ALP-BI was measured by the modified heat-inactivation technique described by Moss & Whitby (1975). This method utilises the different heat stability characteristics of the bone and liver isoenzymes. The total enzyme activity is measured and the presence of significant amounts of ALP from other sources (e.g. gut) excluded by electrophoresis. Serum is incubated at 56°C and at this temperature more than 99% of the bone isoenzyme decays within 15 min. The residual activity of the sample is measured after 15 and 25 min incubation and reflects the inactivation rate of the liver component. The total liver component can be determined by extrapolation from these two measurement and ALP-BI Br.

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New biochemical marker for bone metabolism. Measurement by radioimmunoassay of bone GLA protein in the plasma of normal subjects and patients with bone disease.

Abstract: A B S T R A C T y-

Cited by 637 publications

References 14 publications

miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

miR-34s inhibit osteoblast proliferation and differentiation in the mouse by targeting SATB2

Release of Intact and Fragmented Osteocalcin Molecules from Bone Matrix during Bone Resorption in Vitro

Biochemical prediction of response of bone metastases to treatment

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