ArticleAnnals of the New York Academy of Sciences2018
CTLA-4Ig (abatacept) balances bone anabolic effects of T cells and Wnt-10b with antianabolic effects of osteoblastic sclerostin.
Article in Annals of the New York Academy of Sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
13 citing papers in PubMed, 16 citations in OpenAlex.
- Therapeutic Applications of Immunobiologics in Autoimmune and Inflammatory Diseases.Pharmaceutics · 2026Review
- Biologic immunomodulators and spinal fusion: evidence, mechanisms, and perioperative considerations.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Impact of biologic and targeted synthetic therapies on bone health in immune-mediated inflammatory diseases: a narrative review.Frontiers in medicine · 2026Review
- Combined Sequential Antiretroviral Therapy-Induced Immune Reconstitution Bone Loss and Estrogen Deficiency Bone Loss Are Cumulative in Mice Models.The Journal of infectious diseases · 2025Article
- Preferable effect of CTLA4-Ig on both bone erosion and bone microarchitecture in rheumatoid arthritis revealed by HR-pQCT.Scientific reports · 2024Article
- The role of WNT10B in physiology and disease: A 10-year update.Frontiers in cell and developmental biology · 2023Review
- Cyclic Adenosine Monophosphate (cAMP)-Dependent Phosphodiesterase Inhibition Promotes Bone Anabolism Through CD8JBMR plus · 2022Article
- Article
- Inflammation and Bone Metabolism in Rheumatoid Arthritis: Molecular Mechanisms of Joint Destruction and Pharmacological Treatments.International journal of molecular sciences · 2022Review
- Bone Homeostasis and Gut Microbial-Dependent Signaling Pathways.Journal of microbiology and biotechnology · 2021Review
- Association between serum bone biomarker levels and therapeutic response to abatacept in patients with rheumatoid arthritis (RA): a multicenter, prospective, and observational RA ultrasound cohort study in Japan.BMC musculoskeletal disorders · 2021Observational
- Current Understanding of Osteoimmunology in Certain Osteoimmune Diseases.Frontiers in cell and developmental biology · 2021Review
- Wnt Signaling and Biological Therapy in Rheumatoid Arthritis and Spondyloarthritis.International journal of molecular sciences · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Activated lymphocytes promote inflammation and bone destruction in rheumatoid arthritis (RA), making T cells and B cells therapeutic targets. Indeed, pharmacological blockade of CD28 costimulation using CTLA-4Ig (abatacept), approved for amelioration of RA, renders T cells dormant (anergic). CTLA-4Ig also promotes bone accretion in healthy mice; surprisingly, however, this effect is driven exclusively through upregulation of bone formation, rather than anti-inflammatory effects on resorption. In the study presented here, we utilized T cell receptor β gene and Wnt-10b gene knockout mice to investigate the roles of T cells and Wnt-10b in CTLA-4Ig-induced bone anabolism. Ablation of either T cells or Wnt-10b not only abolished CTLA-4Ig-induced bone anabolism but also, paradoxically, suppressed bone formation leading to bone loss. Stalled bone formation was accompanied by bone marrow stromal cell expression of the Wnt pathway inhibitor sclerostin. Our data suggest that an immunoskeletal pivot may promote or suppress bone formation, depending on the net outcome of CTLA-4Ig action directed independently on T cells and osteoblast-linage cells that counter Wnt-10b-induced bone anabolism, by secretion of sclerostin. While CTLA-4Ig action is tipped in favor of bone formation under physiological conditions, pathological immunodeficiency may lead to suppressed bone formation and skeletal damage.
Indexed as
Identifiers
What OpenQuestion holds
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.