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TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis
Otero K, Shinohara M, Zhao H, Cella M, Gilfillan S, Colucci A, Faccio R, Ross FP et al.. Journal of immunology (Baltimore, Md. : 1950), 2012-02-06
Topic: Brain proteins, microglia and lab models
TREM2 is an immunoreceptor expressed on osteoclasts (OC) and microglia that transmits intracellular signals through the adaptor DAP12. Individuals with genetic mutations inactivating TREM2 or DAP12 develop the Nasu-Hakola disease (NHD) with cystic-like lesions of the bone and brain demyelination that lead to fractures and presenile dementia. The mechanisms of this disease are poorly understood.
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APA 7th
Otero, K., Shinohara, M., Zhao, H., Cella, M., Gilfillan, S., Colucci, A., et al. (2012). TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. Journal of immunology (Baltimore, Md. : 1950). https://doi.org/10.4049/jimmunol.1102836
Vancouver
Otero K, Shinohara M, Zhao H, Cella M, Gilfillan S, Colucci A, et al. TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis. Journal of immunology (Baltimore, Md. : 1950). 2012. doi:10.4049/jimmunol.1102836. PMID: 22312126.
BibTeX
@article{otero2012-22312126,
author = {Otero, K. and Shinohara, M. and Zhao, H. and Cella, M. and Gilfillan, S. and Colucci, A. and Faccio, R. and Ross, F. P. and others},
title = {{TREM2 and β-catenin regulate bone homeostasis by controlling the rate of osteoclastogenesis}},
journal = {Journal of immunology (Baltimore, Md. : 1950)},
year = {2012},
doi = {10.4049/jimmunol.1102836},
pmid = {22312126},
url = {https://doi.org/10.4049/jimmunol.1102836}
}
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Key findings
- Individuals with genetic mutations inactivating TREM2 or DAP12 develop the Nasu-Hakola disease (NHD) with cystic-like lesions of the bone and brain demyelination that lead to fractures and presenile dementia.
- The mechanisms of this disease are poorly understood.
- In this study, we report that TREM2-deficient mice have an osteopenic phenotype reminiscent of NHD.
- In vitro, lack of TREM2 impairs proliferation and β-catenin activation in osteoclast precursors (OcP) in response to M-CSF.
Why it matters
Mice bred without the TREM2 gene had thinner, lower-density bones ("an osteopenic phenotype reminiscent of NHD"), the bone side of Nasu-Hakola disease, an inherited condition that causes bone cysts and early dementia. In lab-dish experiments, cells that become osteoclasts (bone-removing cells) divided less and switched on less β-catenin when they lacked TREM2. This is a mouse and cell study of bone with no brain or Alzheimer's findings, and it tests no treatment.
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Study details
- Evidence strengthLow
How this study scored 50/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of immunology (Baltimore, Md. : 1950)) |
| Journal's citation record | 4 / 4 | The Journal of Immunology: journal h-index 531 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 172 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 10.8 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 3.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 4 / 6 | Cited by 37 other studies in this library |
| Still being cited | 2 / 4 | Cited 41 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Marco Colonna: h-index 172 (OpenAlex, whole career) |
| Institution's track record | 2 / 3 | Washington University in St. Louis: institution h-index 1,962 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 6 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 22312126) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 50 / 100 | — |
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