Evidence map›Paper›PMID 34857734›Full record

ArticleBone research2021

Secreted frizzled related-protein 2 (Sfrp2) deficiency decreases adult skeletal stem cell function in mice.

Luis Fernandez de Castro, Brian J Sworder, Byron Mui, Kathryn Futrega, Agnes Berendsen, Matthew D Phillips, Nathan J Burbach, Natasha Cherman, Sergei Kuznetsov, Yankel Gabet and 2 more

Open access · goldAbstract read
In one paragraph

Article in Bone research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.3field-weighted citation impact, top 20% 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

20 citing papers in PubMed, 27 citations in OpenAlex.

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  12. ER-resident proteins are key players in cartilage and bone homeostasis.Frontiers in cell and developmental biology · 2025
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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

12 authors at 3 institutions in 2 countries.

Luis Fernandez de CastroSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA. luis.fernandezdecastrodiaz@nih.gov.ORCID http://orcid.org/0000-0003-3194-9780
Brian J SworderSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Byron MuiSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Kathryn FutregaSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Agnes BerendsenSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Matthew D PhillipsSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Nathan J BurbachSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Natasha ChermanSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Sergei KuznetsovSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Yankel GabetDepartment of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.
Kenn HolmbeckSkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA.
Pamela G RobeySkeletal Biology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Department of Health and Human Services, National Institutes of Health, Bethesda, MD, USA. pamela.robey@nih.gov.
National Institutes of Health · USBoston University · USTel Aviv University · IL

Funding

The role of stem cells in skeletal health and diseaseZIADE000380 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI ROBEY, PAMELA G · 2009 to 2025
$30.6M
Intramural NIH HHS ZIA DE000380U.S. Department of Health & Human Services | NIH | National Institute of Dental and Craniofacial Research (NIDCR) 1ZIADE000380-36
6 · The paper itself

Abstract

In a previous transcriptomic study of human bone marrow stromal cells (BMSCs, also known as bone marrow-derived "mesenchymal stem cells"), SFRP2 was highly over-represented in a subset of multipotent BMSCs (skeletal stem cells, SSCs), which recreate a bone/marrow organ in an in vivo ectopic bone formation assay. SFRPs modulate WNT signaling, which is essential to maintain skeletal homeostasis, but the specific role of SFRP2 in BMSCs/SSCs is unclear. Here, we evaluated Sfrp2 deficiency on BMSC/SSC function in models of skeletal organogenesis and regeneration. The skeleton of Sfrp2-deficient (KO) mice is overtly normal; but their BMSCs/SSCs exhibit reduced colony-forming efficiency, reflecting low SSC self-renewal/abundancy. Sfrp2 KO BMSCs/SSCs formed less trabecular bone than those from WT littermates in the ectopic bone formation assay. Moreover, regeneration of a cortical drilled hole defect was dramatically impaired in Sfrp2 KO mice. Sfrp2-deficient BMSCs/SSCs exhibited poor in vitro osteogenic differentiation as measured by Runx2 and Osterix expression and calcium accumulation. Interestingly, activation of the Wnt co-receptor, Lrp6, and expression of Wnt target genes, Axin2, C-myc and Cyclin D1, were reduced in Sfrp2-deficient BMSCs/SSCs. Addition of recombinant Sfrp2 restored most of these activities, suggesting that Sfrp2 acts as a Wnt agonist. We demonstrate that Sfrp2 plays a role in self-renewal of SSCs and in the recruitment and differentiation of adult SSCs during bone healing. SFRP2 is also a useful marker of BMSC/SSC multipotency, and a factor to potentially improve the quality of ex vivo expanded BMSC/SSC products.

Identifiers

PMID34857734
PMCPMC8639730
OpenAlexW3217559628

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Registered trials

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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.