Evidence map›Paper›PMID 25491310›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

Acute-phase protein serum amyloid A3 is a novel paracrine coupling factor that controls bone homeostasis.

Roman Thaler, Ines Sturmlechner, Silvia Spitzer, Scott M Riester, Monika Rumpler, Jochen Zwerina, Klaus Klaushofer, Andre J van Wijnen, Franz Varga

Open access · bronzeAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  3. Effect ofAnalytical cellular pathology (Amsterdam) · 2022
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  6. Disease models & mechanisms · 2020
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 5 institutions in 2 countries.

Roman Thaler*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Ines Sturmlechner*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Silvia Spitzer*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Scott M Riester*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Monika Rumpler*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Jochen Zwerina*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Klaus Klaushofer*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA.
Andre J van Wijnen*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA vanwijnen.andre@mayo.edu franz.varga@osteologie.at.
Franz Varga*Ludwig Boltzmann Institute of Osteology, Wiener Gebietskrankenkasse and Allgemeine Unfallversicherungsanstalt, Trauma Center Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; and Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota, USA vanwijnen.andre@mayo.edu franz.varga@osteologie.at.
Ludwig Boltzmann Institute of Osteology · ATAllgemeine Unfallversicherungsanstalt · ATMayo Clinic · USHanusch Hospital · ATMayo Clinic in Arizona · US

Funding

Molecular Control of Bone FormationR01AR049069 · NIAMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI WESTENDORF, JENNIFER J · 2003 to 2021
$5.8M
Austrian Science Fund FWF P 24370NIAMS NIH HHS R01 AR049069NIAMS NIH HHS R01-AR049069
6 · The paper itself

Abstract

Serum amyloid A (A-SAA/Saa3) was shown before to affect osteoblastic metabolism. Here, using RT-quantitative PCR and/or immunoblotting, we show that expression of mouse Saa3 and human SAA1 and SAA2 positively correlates with increased cellular maturation toward the osteocyte phenotype. Expression is not detected in C3H10T1/2 embryonic fibroblasts but is successively higher in preosteoblastic MC3T3-E1 cells, late osteoblastic MLO-A5 cells, and MLO-Y4 osteocytes, consistent with findings using primary bone cells from newborn mouse calvaria. Recombinant Saa3 protein functionally inhibits osteoblast differentiation as reflected by reductions in the expression of osteoblast markers and decreased mineralization in newborn mouse calvaria. Yet, Saa3 protein enhances osteoclastogenesis in mouse macrophages/monocytes based on the number of multinucleated and tartrate-resistant alkaline phosphatase-positive cells and Calcr mRNA expression. Depletion of Saa3 in MLO osteocytes results in the loss of the mature osteocyte phenotype. Recombinant osteocalcin, which is reciprocally regulated with Saa3 at the osteoblast/osteocyte transition, attenuates Saa3 expression in MLO-Y4 osteocytes. Mechanistically, Saa3 produced by MLO-Y4 osteocytes is integrated into the extracellular matrix of MC3T3-E1 osteoblasts, where it associates with the P2 purinergic receptor P2rx7 to stimulate Mmp13 expression via the P2rx7/MAPK/ERK/activator protein 1 axis. Our data suggest that Saa3 may function as an important coupling factor in bone development and homeostasis.

Indexed as

3T3 CellsAmino Acid SequenceAnimalsAnimals, NewbornBone and BonesCell DifferentiationCell LineCells, CulturedHomeostasisHumansMatrix Metalloproteinase 13MiceMice, Inbred C57BLMolecular Sequence DataOsteoblastsOsteocalcinMatrix Metalloproteinase 13Mmp13 protein, mouseOsteocalcinP2rx7 protein, mouseReceptors, Purinergic P2X7RNA, Small InterferingSAA1 protein, humanSAA2 protein, humanSaa3 protein, mouseSerum Amyloid A Proteinosteoblastosteoclastosteocyteosteogenesis

Identifiers

PMID25491310
PMCPMC4396610
OpenAlexW2071278845

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.