ArticleJCI insight2022
A single-cell mass cytometry platform to map the effects of preclinical drugs on cartilage homeostasis.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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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.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Immune profiling in orthopaedic diseases using mass cytometry : a narrative review of applications and future directions.Bone & joint research · 2026Article
- Mechanism driven adaptation of smart hydrogels to the osteoarthritis pathological microenvironment.Frontiers in bioengineering and biotechnology · 2026Review
- Can alternatives to animal testing yield useful information regarding biological mechanisms and drug discovery?Journal of orthopaedic translation · 2025Review
- The Senotherapeutic Effects of APPA (Apocynin [AP] and Paeonol [PA]) on Senescent Human Chondrocytes.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Insights into chondrocyte populations in cartilaginous tissues at the single-cell level.Nature reviews. Rheumatology · 2025Review
- Transformative approaches for effective clinical trials to reduce the disease burden of osteoarthritis.Seminars in arthritis and rheumatism · 2025Review
- Osteoarthritis.Nature reviews. Disease primers · 2025Review
- Multiparametric identification of putative senescent cells in skeletal muscle via mass cytometry.Cytometry. Part A : the journal of the International Society for Analytical Cytology · 2024Article
- Aging and the emerging role of cellular senescence in osteoarthritis.Osteoarthritis and cartilage · 2024Review
- Three decades of advancements in osteoarthritis research: insights from transcriptomic, proteomic, and metabolomic studies.Osteoarthritis and cartilage · 2024Review
- Profiling joint tissues at single-cell resolution: advances and insights.Nature reviews. Rheumatology · 2024Review
- JD-312 - A novel small molecule that facilitates cartilage repair and alleviates osteoarthritis progression.Journal of orthopaedic translation · 2024Article
- Recent advancements in single-cell metabolic analysis for pharmacological research.Journal of pharmaceutical analysis · 2023Review
- Application of Single-Cell and Spatial Omics in Musculoskeletal Disorder Research.International journal of molecular sciences · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
No disease-modifying drug exists for osteoarthritis (OA). Despite success in animal models, candidate drugs continue to fail in clinical trials owing to the unmapped interpatient heterogeneity and disease complexity. We used a single-cell platform based on cytometry by time-of-flight (cyTOF) to precisely outline the effects of candidate drugs on human OA chondrocytes. OA chondrocytes harvested from patients undergoing total knee arthroplasty were treated with 2 drugs, an NF-κB pathway inhibitor, BMS-345541, and a chondroinductive small molecule, kartogenin, that showed preclinical success in animal models for OA. cyTOF conducted with 30 metal isotope-labeled antibodies parsed the effects of the drugs on inflammatory, senescent, and chondroprogenitor cell populations. The NF-κB pathway inhibition decreased the expression of p-NF-κB, HIF2A, and inducible NOS in multiple chondrocyte clusters and significantly depleted 4 p16ink4a-expressing senescent populations, including NOTCH1+STRO1+ chondroprogenitor cells. While kartogenin also affected select p16ink4a-expressing senescent clusters, there was a less discernible effect on chondroprogenitor cell populations. Overall, BMS-345541 elicited a uniform drug response in all patients, while only a few responded to kartogenin. These studies demonstrate that a single-cell cyTOF-based drug screening platform can provide insights into patient response assessment and patient stratification.
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Registered trials
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.