ArticleCell stem cell2023
Lgr5-expressing secretory cells form a Wnt inhibitory niche in cartilage critical for chondrocyte identity.
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Article in Cell stem cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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26citing papers in PubMed
9.9field-weighted citation impact, top 1% of its field
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- TGFBI Maintains Fibrocartilage Homeostasis by Restraining O-GlcNAcylation to Inactivate and Destabilize ADAMTS16 in Temporomandibular Joint Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sensory nerve-derived signaling coordinates oropharyngeal structural organization that supports suckling and vocalization in neonatal mice.Nature communications · 2026Article
- Mechanical Overloading-Induced Nanomineral Crystal Perturbation from the Osteochondral Interface: A Potential Initiator of Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Identification of synovial lymphatic system in the temporomandibular joint and their roles in arthritis and pain.Nature communications · 2026Article
- Article
- Reduced cartilage matrix stiffness in temporomandibular joint osteoarthritis impairs the functions of superficial zone chondrocytes via downregulation of CREB5-PLPP3 signaling.Molecular biomedicine · 2026Article
- Identification of a putative progenitor-like chondrocyte subpopulation in osteoarthritic human cartilage.Stem cell research & therapy · 2026Article
- Stage-resolved geography of mouse skeletal stem cells.Journal of bone and mineral metabolism · 2026Review
- Spatial Transcriptomics of TMJ Reveals a Remodeling Fibroblast-Immune Microenvironment Driving Arthritis Pain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Bridging Temporomandibular Joint Structure, Function, and Pain: An Integrated Multiscale Perspective.Journal of dental research · 2026Review
- Injectable hydrogel microspheres delivering cartilage-targeted LGR5-engineered exosomes for osteoarthritis therapy.Materials today. Bio · 2026Article
- Multiscale 3D Whole Joint Cellular and Molecular Mapping Reveals Disease-Specific Neurovascular Plasticity Underlying the Structure-Pain Relationship.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Multimodal modulation of metal-based nanomaterials in osteoarthritis immunotherapy: current landscape and future paradigms.Frontiers in immunology · 2026Review
- A bio-adaptive physical hydrogel enables dynamic tissue engineering for tracheal reconstruction.Nature communications · 2025Article
- Controlled Release of Human Dental Pulp Stem Cell-Derived Exosomes from Hydrogels Attenuates Temporomandibular Joint Osteoarthritis.Advanced healthcare materials · 2025Article
- Preclinical perspectives on disorders of the temporomandibular joint: Tracing the past, navigating the present, and shaping the future.The journal of pain · 2025Review
- Primary cilia in growth plates orchestrate long bone development.Fundamental research · 2025Article
- DDX1 methylation mediated MATR3 splicing regulates intervertebral disc degeneration by initiating chromatin reprogramming.Nature communications · 2025Article
- Identification of Synovial Lymphatics in the TMJ and their Roles in Arthritis and Pain.Research square · 2025Article
- Stem and progenitor cells in the synovial joint as targets for regenerative therapy.Nature reviews. Rheumatology · 2025Review
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Authors and funding
19 authors at 5 institutions in 2 countries.
Angela RuscittoCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA.
Peng ChenClemson University-Medical University of South Carolina Joint Bioengineering Program, Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Ikue TosaCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ziyi WangDepartment of Molecular Biology and Biochemistry, Okayama University Graduate, School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008525, Japan.
Gan ZhouCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ingrid SafinaCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Ran WeiCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Mallory M MorelCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Alia KochSection of Hospital Dentistry, Division of Oral & Maxillofacial Surgery, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Michael FormanSection of Hospital Dentistry, Division of Oral & Maxillofacial Surgery, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA.
Gwendolyn ReeveDivision of Oral and Maxillofacial Surgery, New York Presbyterian Weill Cornell Medicine, New York, NY 10065, USA.
Michael K LecholopDepartment of Oral and Maxillofacial Surgery, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Marshall WilsonClemson University-Medical University of South Carolina Joint Bioengineering Program, Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Daniel BonthiusClemson University-Medical University of South Carolina Joint Bioengineering Program, Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Mo ChenWnt Scientific, LLC, Harlem Biospace, New York, NY 10027, USA.
Mitsuaki OnoDepartment of Molecular Biology and Biochemistry, Okayama University Graduate, School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 7008525, Japan; Department of Oral Rehabilitation and Implantology, Okayama University Hospital, Okayama 7008525, Japan.
Timothy C WangColumbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA; Division of Digestive and Liver Diseases, Department of Medicine, College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY 10032, USA.
Hai YaoClemson University-Medical University of South Carolina Joint Bioengineering Program, Department of Bioengineering, Clemson University, Clemson, SC 29634, USA; Department of Oral Health Sciences, College of Dental Medicine, Medical University of South Carolina, Charleston, SC 29425, USA.
Mildred C EmbreeCartilage Biology and Regenerative Medicine Laboratory, Section of Growth and Development, Division of Orthodontics, College of Dental Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA; Columbia Stem Cell Initiative, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: mce2123@cumc.columbia.edu.
Columbia University Irving Medical Center · USMedical University of South Carolina · USOkayama University · JPCornell University · USHarlem United · US
Funding
Tissue Structural and Neural Remodeling in Human Sacroiliac JointP20GM121342 · NIGMS · CLEMSON UNIVERSITY · PI Peng Chen · 2018 to 2026
$24.7MT-COHR: Training in Craniofacial and Oral Health ResearchT32DE017551 · NIDCR · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI YAO, HAI · 2006 to 2025
$10.3MThe Role of Stem Cells and the Microenvironment in Gastrointestinal CancersR35CA210088 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Timothy Cragin Wang · 2017 to 2026
$10.2MIntegrating craniofacial morphology, oral function, temporomandibular biomechanics and mechanobiology to determine sex-specific TMJ pathophysiology in humansR01DE021134 · NIDCR · CLEMSON UNIVERSITY · PI YAO, HAI · 2012 to 2025
$4.7MImprovement of Animal Models for TMJ Stem Cell-Based RegenerationR01DE029068 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI EMBREE, MILDRED CHRISTINE · 2019 to 2023
$3.6MDevelopment of Drug Delivery Technology for Stem Cell Based TMJ RegenerationR42DE028215 · NIDCR · WNT SCIENTIFIC, LLC · PI CHEN, MO, EMBREE, MILDRED CHRISTINE · 2020 to 2021
$1.5MNIDCR Dentist Scientist K99:Improve TMJ Fibrocartilage Regeneration StrategiesR00DE022060 · NIDCR · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI EMBREE, MILDRED CHRISTINE · 2014 to 2018
$1.2MDevelopment of Drug Delivery Technology for Stem Cell-Based TMJ RegenerationR41DE028215 · NIDCR · WNT SCIENTIFIC, LLC · PI CHEN, MO, EMBREE, MILDRED CHRISTINE · 2018 to 2018
$225kAnalysis of the rib construct for treatment of early-onset spinal deformity with hyperkyphosisF31AR076917 · NIAMS · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI BONTHIUS, DANIEL JAMES · 2020 to 2021
$92kNCI NIH HHS R35 CA210088NIAMS NIH HHS F31 AR076917NIDCR NIH HHS R00 DE022060NIDCR NIH HHS R01 DE021134NIDCR NIH HHS R01 DE029068NIDCR NIH HHS R41 DE028215NIDCR NIH HHS R42 DE028215NIDCR NIH HHS T32 DE017551NIGMS NIH HHS P20 GM121342
Abstract
Osteoarthritis is a degenerative joint disease that causes pain, degradation, and dysfunction. Excessive canonical Wnt signaling in osteoarthritis contributes to chondrocyte phenotypic instability and loss of cartilage homeostasis; however, the regulatory niche is unknown. Using the temporomandibular joint as a model in multiple species, we identify Lgr5-expressing secretory cells as forming a Wnt inhibitory niche that instruct Wnt-inactive chondroprogenitors to form the nascent synovial joint and regulate chondrocyte lineage and identity. Lgr5 ablation or suppression during joint development, aging, or osteoarthritis results in depletion of Wnt-inactive chondroprogenitors and a surge of Wnt-activated, phenotypically unstable chondrocytes with osteoblast-like properties. We recapitulate the cartilage niche and create StemJEL, an injectable hydrogel therapy combining hyaluronic acid and sclerostin. Local delivery of StemJEL to post-traumatic osteoarthritic jaw and knee joints in rabbit, rat, and mini-pig models restores cartilage homeostasis, chondrocyte identity, and joint function. We provide proof of principal that StemJEL preserves the chondrocyte niche and alleviates osteoarthritis.
Indexed as
ChondrocytesOsteoarthritisAgingAnimalsCartilageRabbitsRatsReceptors, G-Protein-CoupledSwineSwine, MiniatureReceptors, G-Protein-Coupledarticular cartilagebiomaterialschondroprogenitor cellshydrogelsLgr5osteoarthritisregenerationskeletal developmentstem cell nichesynovial jointtemporomandibular jointWNT signaling
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