Structure, Activity, and Distribution of Fish Osteocalcin

Nishimoto, Satoru K.; Waite, J. Herbert; Nishimoto, Miyako; Kriwacki, Richard W.

doi:10.1074/jbc.m211449200

Cited by 50 publications

(29 citation statements)

References 17 publications

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“…Such departure from the stronger conservation evident in higher vertebrates may represent the differing requirements for salt and water homeostasis in fish. Furthermore, differences in the cellularity of bone, such as osteocyte numbers and, thus, skeletal physiology, may further explain the absence of Ostn in Fugu (24,25).…”

Section: Discussionmentioning

confidence: 99%

Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth

Moffatt

Thomas

Sellin

et al. 2007

Journal of Biological Chemistry

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Osteocrin (Ostn) is a recently discovered secreted protein produced by cells of the osteoblast lineage that shows a well conserved homology with members of the natriuretic peptide (NP) family. We hypothesized that Ostn could interact with the NP receptors, thereby modulating NP actions on the skeleton. Ostn binds specifically and saturably to the NP peptide receptor-C (NPR-C) receptor with a K d of ϳ5 nM with no binding to the GC-A or GC-B receptors. Deletion of several of the residues deemed important for NP binding to NPR-C led to abolition of Ostn binding, confirming the presence of a "natriuretic motif." Functionally, Ostn was able to augment C-type natriuretic peptide-stimulated cGMP production in both pre-chondrocytic (ATDC5) and osteoblastic (UMR106) cells, suggesting increased NP levels due to attenuation of NPR-C associated NP clearance. Ostn-transgenic mice displayed elongated bones and a marked kyphosis associated with elevated bone cGMP levels, suggesting that elevated natriuretic peptide activity contributed to the increased bone length possibly through an increase in growth plate chondrocyte proliferation. Thus, we have demonstrated that Ostn is a naturally occurring ligand of the NPR-C clearance receptor and may act to locally modulate the actions of the natriuretic system in bone by blocking the clearance action of NPR-C, thus locally elevating levels of C-type natriuretic peptide. Osteocrin (Ostn)3 is a recently discovered novel small secreted protein with prohormone-like characteristics (1). To date, the exact role of Ostn has not been elucidated. Limited homology, however, was observed between Ostn and members of the natriuretic peptide family, suggesting a possible functional link. The natriuretic system, key in the maintenance of vascular tone and cardiovascular homeostasis, consists of three related natriuretic peptides (NPs), ANP, BNP, and CNP (2) and three receptors (NPRs) mediating the biological activity of these peptides. The GC-A receptor, which preferentially binds ANP and BNP, and the GC-B receptor, whose cognate ligand is CNP, are coupled to guanylyl cyclase, producing cGMP as a secondary messenger (3, 4). The third receptor, NPR-C, has no guanylyl cyclase activity and binds all three NPs with similar affinity (5). To date, no specific endogenous ligand has been identified for NPR-C, and it is thought to act mainly as a clearance receptor (6). However, other biological functions have been postulated for this receptor (6).A number of recent reports have demonstrated that the NPs also play a key role in regulation of the skeleton (7). Mice overexpressing either BNP (8) or CNP (9) or lacking NPR-C (10) display elongated bones, whereas mice lacking CNP (11) or a functional GC-B receptor exhibit dwarfism (12). Interestingly, we initially identified Ostn in cells of the osteoblast lineage, the bone-producing cells, which together with its regulatory effects on these cells suggested a role in bone activity. Given the homology of Ostn to the NP family and its putative bone regulatory actio...

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Section: Discussionmentioning

confidence: 99%

Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth

Moffatt

Thomas

Sellin

et al. 2007

Journal of Biological Chemistry

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“…a, mouse osteocalcin genes form a cluster where each gene has the same pattern. b, gene structure predicted from in silico analysis (9).…”

Section: Cloning Of Spotted Green Pufferfish Osteocalcin Cdna and Gene-mentioning

confidence: 99%

“…Nishimoto and colleagues (9) have recently reported osteocalcin gene and cDNA structures for two pufferfish (Takifugu rubripes and Tetraodon nigroviridis) based on computer analysis of the genomic sequences retrieved from public data bases. Surprisingly, the size of putative exon 2 in these species was much smaller than those observed for other species (including fish; Fig.…”

mentioning

confidence: 99%

Identification of an Osteocalcin Isoform in Fish with a Large Acidic Prodomain

Laizé

Viegas

Price

et al. 2006

Journal of Biological Chemistry

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Osteocalcin is a small, secreted bone protein whose gene consists of four exons. In the course of analyzing the structure of fish osteocalcin genes, we recently found that the spotted green pufferfish has two possible exon 2 structures, one of 15 bp and the other of 324 bp. Subsequent analysis of the pufferfish cDNA showed that only the transcript with a large exon 2 exists. Exon 2 codes for the osteocalcin propeptide, and exon 2 of pufferfish osteocalcin is ϳ3.4-fold larger than exon 2 previously found in other vertebrate species. We have termed this new pufferfish osteocalcin isoform OC2. Additional studies showed that the OC2 isoform is restricted to a unique fish taxonomic group, the Osteichthyes; OC2 is the only osteocalcin isoform found so far in six Osteichthyes species, whereas both OC1 and OC2 isoforms coexist in zebrafish and rainbow trout. The larger size of the OC2 propeptide is due to an acidic region that is likely to be highly phosphorylated and has no counterpart in the OC1 propeptide. We propose 1) that OC1 and OC2 are encoded by distinct genes that originated from a duplication event that probably occurred in the teleost fish lineage soon after divergence from tetrapods and 2) that the novel OC2 propeptide could be, if secreted, a phosphoprotein that participates in the regulation of biomineralization through its large acidic and phosphorylated propeptide.

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“…Jung [6,7] separated and obtained two calcium binding active peptides from the hoki (Johnius belengerii) bone and the Alaska Pollack backbone and found that they contain abundant Thr, Tyr, and Ser. Nishimoto [37] purified carp bone and obtained osteocalcin, which has high ratios of Ala, Tyr, Thr, Gln, and Asp. Jiang [35] prepared phosphopeptides from hen egg yolk phosvitin, which is composed mainly of Ser, Asx, Glx, and Arg.…”

Section: Isolation and Purification Of Calcium Binding Peptidesmentioning

confidence: 99%

Purification of Bovine Bone Oligophosphopeptide with High Calcium-binding Activity by <i>Bacillus cereus </i>MBL13 Collagenolytic Protease

Liu¹,

Yang²,

Zhu³

et al. 2017

JFNR

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A demineralized bovine bone was hydrolyzed by a specific bone-degrading collagenolytic protease extracted from Bacillus cereus MBL13 (isolated from chopped animal bone wastes) to utilize its collagen in nutraceuticals with high calcium bioavailability. Bovine bone peptide (BBP), a novel oligophosphopeptide with a high calcium binding ability (8.25 mmol/g-protein), was isolated from bovine bone hydrolysates by Chelex 100, ultrafiltration, hydroxyapatite chromatography, gel filtration chromatography, and reverse-phase high performance liquid chromatography. The results showed that demineralization treatment can significantly increase hydrolysis (p < 0.05). The amino acid content of BBP showed that the Asp, Ala, Tyr, and Thr contents were remarkable increments compared to the bone hydrolysates. The molecular mass of BBP was found to be around 3.305 kDa through SDS-PAGE and MALDI-TOF mass spectrometry. FT-IR spectra showed characteristic absorption peaks. Moreover, BBP exhibited higher calcium binding activity than that of casein oligophosphopeptide (CPP). Therefore, this study demonstrated that B. cereus MBL13 collagenolytic protease (BCC) could degrade bovine bone collagen, and prepared oligophosphopeptide could be utilized as a nutraceutical with high calcium-binding activity.

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Structure, Activity, and Distribution of Fish Osteocalcin

Cited by 50 publications

References 17 publications

Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth

Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth

Identification of an Osteocalcin Isoform in Fish with a Large Acidic Prodomain

Purification of Bovine Bone Oligophosphopeptide with High Calcium-binding Activity by <i>Bacillus cereus </i>MBL13 Collagenolytic Protease

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