ArticleCell2015
Gremlin 1 identifies a skeletal stem cell with bone, cartilage, and reticular stromal potential.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06354023 (Administration of Recombinant Human Growth Hormone in the Knee Joint of Patients Suffering from Osteoarthritis), which is not on this map. Cited by 421 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
421citing papers in PubMed, 1 pooled it
38.6field-weighted citation impact, top 1% of its field
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.
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.
Administration of Recombinant Human Growth Hormone in the Knee Joint of Patients Suffering from Osteoarthritis
Who cites it
421 citing papers in PubMed, 1 synthesis or guideline pooled it, 644 citations in OpenAlex.
- Stem cell injections for osteoarthritis of the knee.The Cochrane database of systematic reviews · 2025Pooled it
- Stem cell senescence as a regenerative bottleneck in age-related skeletal degeneration: Mechanistic crosstalk and translational strategies.Regenerative therapy · 2026Review
- Single-cell RNA sequencing reveals chondrocyte heterogeneity and fibrocartilage transition in osteonecrosis of the femoral head.iScience · 2026Article
- Spatial transcriptomic atlas of aggressive osteosarcomas reveals shared immune landscape and targetable surface markers.Nature communications · 2026Article
- An ITGA11 expressing subpopulation as predictor for the donor-specific osteogenic capacity of stromal cells.Bone research · 2026Article
- A tissue engineering approach to regenerate the cranial suture skeletal stem cell niche with a multicompartment biomaterial scaffold.Bone research · 2026Article
- Intermittent parathyroid hormone employs autonomous and non-autonomous mechanisms to drive osteogenesis from Ebf3-expressing skeletal progenitor cells.bioRxiv : the preprint server for biology · 2026Article
- Targeting Wnt/β-catenin and circadian regulator restores PRC2/EZH2-controlled chromatin bivalency and suppresses cell state diversity.The Journal of clinical investigation · 2026Article
- Type E endothelial cells orchestrate embryonic skeletogenesis via chondrogenic priming of skeletal progenitors.Journal of orthopaedic translation · 2026Article
- The role of Pth1r in posterior cranium cartilage regulation and craniosynostosis.Nature communications · 2026Article
- Stage-resolved geography of mouse skeletal stem cells.Journal of bone and mineral metabolism · 2026Review
- Overcoming challenges in cartilage regeneration: The role of chondrogenic inducers.Bioengineering & translational medicine · 2026Review
- Inflammation perturbs hematopoiesis by remodeling specific compartments of the bone marrow niche.Blood · 2026Article
- Modeling the chondrocyte-derived osteoblasts formation process reveals its molecular signature and regulation network.Bone research · 2026Article
- LOXL2 deletion triggers TMJ osteoarthritis, while overexpression protects it from NF-κB-induced chondrocyte apoptosis.International journal of oral science · 2026Article
- Article
- A paracrine-to-autocrine shunt of GREM1 fuels colorectal cancer metastasis via ACVR1C.Molecular cancer · 2026Article
- Beyond resorption-driven coupling: a multi-layered framework for osteoclast-osteoblast communication and its therapeutic consequences.Frontiers in endocrinology · 2026Review
- Ferroptosis in osteoporosis: core mechanisms, cell-specific effects in bone remodelling, and therapeutic perspectives.Frontiers in endocrinology · 2026Review
- Surface marker-defined functional subpopulations of mesenchymal stromal cells: mechanisms, applications, and clinical translation.Frontiers in bioengineering and biotechnology · 2026Review
361 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
51 authors at 12 institutions in 5 countries.
Daniel L WorthleyDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA; Department of Medicine, University of Adelaide, SA, 5005, Australia; Cancer theme, South Australian Health and Medical Research Institute, SA, 5001, Australia; Murdoch Children's Research Institute, Royal Children's Hospital, Vic., 3052, Australia.
Michael ChurchillDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Jocelyn T ComptonDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Yagnesh TailorDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Meenakshi RaoDepartment of Pediatrics, Columbia University, New York, NY 10032, USA.
Yiling SiDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Daniel LevinChildren's Hospital Los Angeles, Saban Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90027, USA.
Matthew G SchwartzDepartment of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Aysu UygurDepartment of Genetics, Harvard Medical School, Boston, MA 02114, USA.
Yoku HayakawaDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Stefanie GrossDepartment of Genetics and Development, Columbia University, New York, NY 10032, USA.
Bernhard W RenzDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Wanda SetlikDepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Ashley N MartinezDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Xiaowei ChenDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Saqib NizamiDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Heon Goo LeeDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
H Paco KangDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Jon-Michael CaldwellDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Samuel AsfahaDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
C Benedikt WestphalenDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA; Department of Internal Medicine III, University Hospital Munich, Ludwig-Maximilians-University Munich - Campus Groβhadern, Munich 81377, Germany.
Trevor GrahamBarts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
Guangchun JinDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Karan NagarDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Hongshan WangDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Mazen A KheirbekDepartment of Psychiatry, Columbia University, New York, NY 10032, USA.
Alka KolheDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Jared CarpenterDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Mark GlaireDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Abhinav NairDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Simon RendersDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Nicholas ManieriDepartment of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
Sureshkumar MuthupalaniDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
James G FoxDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Maximilian ReichertDivision of Gastroenterology, Departments of Medicine and Genetics, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Andrew S GiraudMurdoch Children's Research Institute, Royal Children's Hospital, Vic., 3052, Australia.
Robert F SchwabeDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA.
Jean-Phillipe PradereDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA; Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paul Sabatier, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC)- UMR1048, Toulouse 31432, France.
Katherine WaltonDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Ajay PrakashDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Deborah GumucioDepartment of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA.
Anil K RustgiDivision of Gastroenterology, Departments of Medicine and Genetics, Abramson Cancer Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Thaddeus S StappenbeckDepartment of Pathology and Immunology, Washington University, St. Louis, MO 63110, USA.
Richard A FriedmanHerbert Irving Comprehensive Cancer Center Biomedical Informatics Shared Resource and Department of Biomedical Informatics, Columbia University, New York, NY 10032, USA.
Michael D GershonDepartment of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
Peter SimsDepartment of Systems Biology, Columbia University, NY, 10032, USA.
Tracy GrikscheitChildren's Hospital Los Angeles, Saban Research Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA 90027, USA.
Francis Y LeeDepartment of Orthopedic Surgery, Columbia University Medical Center, New York, NY 10032, USA.
Gerard KarsentyDepartment of Genetics and Development, Columbia University, New York, NY 10032, USA.
Siddhartha MukherjeeDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA. Electronic address: sm3252@columbia.edu.
Timothy C WangDepartment of Medicine and Irving Cancer Research Center, Columbia University, New York, NY 10032, USA. Electronic address: tcw21@columbia.edu.
Columbia University · USCancer Research Center · USColumbia University Irving Medical Center · USUniversity of Michigan · USHarvard University · USMassachusetts Institute of Technology · USUniversity of Pennsylvania · USUniversity of Southern California · USWashington University in St. Louis · USLudwig-Maximilians-Universität München · DEQueen Mary University of London · GBRoyal Children's Hospital · AU
Funding
TOXICOLOGY CORE UNITP30ES002109 · NIEHS · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI LEVINE, STUART S · 1985 to 2020
$25.6MCELLULAR AND MOLECULAR BIOLOGY AT MICHIGANT32GM007315 · NIGMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PUTHENVEEDU, MANOJKUMAR A · 1985 to 2021
$12.8MMICROENVIRONMENT IN ENTERIC NEURON DEVELOPMENTR01NS015547 · NINDS · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI GERSHON, MICHAEL D, MARGOLIS, KARA GROSS · 1985 to 2022
$7.2MThe Role of Inflammation and Stroma in Digestive CancerU54CA126513 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI TYCKO, BENJAMIN · 2006 to 2010
$5.1MERK Signaling in Inflammatory Bone LossR01AR056246 · NIAMS · YALE UNIVERSITY · PI LEE, FRANCIS YOUNG-IN · 2009 to 2018
$3.5MMechanobiological Mechanism for Inflammatory Bone LossR01EB006834 · NIBIB · YALE UNIVERSITY · PI LEE, FRANCIS YOUNG-IN · 2007 to 2015
$2.6MYes1 as a quiescence regulator in hematopoietic stem cellsR01HL115145 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MUKHERJEE, SIDDHARTHA · 2013 to 2017
$2.0MNCI NIH HHS 5U54 CA126513NCI NIH HHS U54 CA126513NHLBI NIH HHS R01 HL115145NIAMS NIH HHS AR056246NIAMS NIH HHS R01 AR056246NIBIB NIH HHS EB006834NIBIB NIH HHS R01 EB006834NIEHS NIH HHS P30 ES002109NIGMS NIH HHS T32 GM007315NINDS NIH HHS R01 NS015547PHS HHS R01 RHL115145A
Abstract
The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).
Indexed as
AnimalsBone and BonesCartilageCytokinesIntercellular Signaling Peptides and ProteinsIntestine, SmallMesenchymal Stem CellsMiceMice, Inbred C57BLCytokinesGrem1 protein, mouseIntercellular Signaling Peptides and Proteins
Identifiers
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Read underepoch 390
Registered trials
NCT06354023ClinicalTrials.gov
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.