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p75<sup>NTR</sup> orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis.

Overview

Authors: Chiho Kadota-Watanabe1,2,3, Jinsook Suh1, Eric Yin1, Byron Zhao1, Jey Kim1, Yan Zhang1, In-Won Chang4, Sowmya Ramesh5, Yuna Lee1, Joshua Chen1, Maulik Ahuja1, Sara Jahangiri1, Isabelle Lao-Ngo1, Ursula Eisinger1, Kate Lindsey1, Haihui Zhang1, Fatemeh Momen-Heravi1,6, Juan Du7, James M Gardner7, Rebeka Silva8
and 6 other authorsSumit Yadav9, Chelsea S Bahney3,10, Aaron W James5, Reuben H Kim4, Ophir D Klein1,11, Christine Hong1,12
ORCID iDs: Chiho Kadota-Watanabe, Jinsook Suh, Eric Yin, Jey Kim, Sowmya Ramesh, Yuna Lee, Isabelle Lao-Ngo, Kate Lindsey, Haihui Zhang, Fatemeh Momen-Heravi, James M Gardner, Chelsea S Bahney, Aaron W James, Ophir D Klein, Christine Hong
  1. Department of Orofacial Sciences, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
  2. Department of Maxillofacial Orthognathics, Division of Maxillofacial and Neck Reconstruction, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo, Tokyo, Japan
  3. Orthopaedic Trauma Institute, University of California, San Francisco, San Francisco, CA, USA
  4. The Shapiro Family Laboratory of Viral Oncology and Aging Research, School of Dentistry, University of California, Los Angeles, Los Angeles, CA, USA
  5. Department of Pathology, Johns Hopkins University, Baltimore, MD, USA
  6. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA
  7. Department of Surgery, UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA, USA
  8. Oral and Maxillofacial Surgery, School of Dentistry, University of California, San Francisco, San Francisco, CA, USA
  9. Department of Growth and Development, University of Nebraska Medical Center, Omaha, NE, USA
  10. Center for Regenerative Medicine, Steadman Philippon Research Institute, Vail, CO, USA
  11. Department of Pediatrics, Cedars-Sinai Guerin Children’s, Los Angeles, CA, USA
  12. Department of Orthodontics, School of Dentistry, University of Washington, Seattle, WA, USA
Institutions: University of California, San Francisco (United States); Institute of Science Tokyo (Japan); University of California, Los Angeles (United States); Johns Hopkins University (United States); UCSF Helen Diller Family Comprehensive Cancer Center (United States); University of San Francisco (United States); Nebraska Medical Center (United States); University of Nebraska Medical Center (United States); Steadman Philippon Research Institute (United States); Cedars-Sinai Medical Center (United States); University of Washington (United States)
Journal: Science advances, volume 12, issue 43, article eaef7786
Dates: received 23 January 2026; accepted 22 September 2026; published online 21 October 2026; in print October 2026
Type: Research article · Language: English
License: CC BY-NC
Identifiers: DOI 10.1126/sciadv.aef7786 · PMID 42905810 · PMCID PMC13685922 · OpenAlex W7223107283
Open access: gold, a free copy (OpenAlex)
Status: data only (how the code is found and verified)
Categories: human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions
MeSH: Chondrogenesis*, Homeostasis*, Nerve Tissue Proteins*, Receptors, Nerve Growth Factor*, Temporomandibular Joint*, Animals, Brain-Derived Neurotrophic Factor, Cell Differentiation, Chondrocytes, Humans, Mandibular Condyle, Mice, p38 Mitogen-Activated Protein Kinases, Signal Transduction (* major topic)
Topic: Osteoarthritis Treatment and Mechanisms (Rheumatology, Medicine), according to OpenAlex
Funding: National Institute of Arthritis and Musculoskeletal and Skin Diseases; National Institute of Dental and Craniofacial Research
Citations: not cited yet (Europe PMC); 73 references in the paper

Abstract

The temporomandibular joint (TMJ) is essential for oral functions such as chewing, speaking, and swallowing. Temporomandibular disorders that impair these functions notably reduce patients’ quality of life, and few therapeutic strategies are available to ameliorate these conditions. Here, we identify the neurotrophin receptor (p75NTR) as a central regulator of mandibular condylar cartilage development, mechanoadaptation, and homeostasis. p75NTR loss causes condylar and disc hypoplasia, reduced chondrocyte number, impaired load-induced anabolism, and accelerated degeneration. Conditional deletion experiments demonstrate chondrocyte-autonomous requirements for the brain-derived neurotrophic factor (BDNF)–p75NTR axis, which activates phosphoinositide 3-kinase AKT serine/threonine kinase and p38 mitogen-activated protein kinase signaling to promote proliferation and chondrogenic differentiation while restraining apoptosis. Degenerative human condyles exhibit reduced p75NTR expression levels. Together, these data establish p75NTR as a molecular hub integrating neurotrophic and mechanical cues to preserve postnatal TMJ architecture and highlight the BDNF-p75NTR axis as a potential therapeutic target.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Code

The paper links to its data and to no code of its authors: see the Data section.

The paper's code and data availability statement is in the Data section.

Tracing map

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Data

Datasets cited

Data, code, and materials availability

All data and code needed to evaluate and reproduce the results in the paper are present in the paper and/or the Supplementary Materials. Source data underlying the quantitative analyses in the main and supplementary figures are provided in data S1. Bulk RNA-seq data have been deposited in Figshare under accession number 10.6084/m9.figshare.30809450 (http://dx.doi.org/10.6084/m9.figshare.30809450). scRNA-seq data have been deposited in the Gene Expression Omnibus (GEO) under accession number GSE313304 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313304) (https://ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE313304). Mouse strains used in this study are commercially available from The Jackson Laboratory (https://jax.org/jax-mice-and-services/find-mice). No custom software was developed; data analyses were performed using publicly available R packages as described in Materials and Methods. This study did not generate new materials.

Reproduced under the paper's license (CC BY-NC), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 25 October 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 26 authors, 14 MeSH terms, 2 funders, 73 references.

Cite

This paper

Kadota-Watanabe, C., Suh, J., Yin, E., Zhao, B., Kim, J., Zhang, Y., Chang, I.-W., Ramesh, S., Lee, Y., Chen, J., Ahuja, M., Jahangiri, S., Lao-Ngo, I., Eisinger, U., Lindsey, K., Zhang, H., Momen-Heravi, F., Du, J., Gardner, J. M., . . . Hong, C. (2026). p75<sup>NTR</sup> orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis. Science advances, 12(43), eaef7786. https://doi.org/10.1126/sciadv.aef7786

BibTeX

@article{kadotawatanabe2026p75,
author = {Kadota-Watanabe, Chiho and Suh, Jinsook and Yin, Eric and Zhao, Byron and Kim, Jey and Zhang, Yan and Chang, In-Won and Ramesh, Sowmya and Lee, Yuna and Chen, Joshua and Ahuja, Maulik and Jahangiri, Sara and Lao-Ngo, Isabelle and Eisinger, Ursula and Lindsey, Kate and Zhang, Haihui and Momen-Heravi, Fatemeh and Du, Juan and Gardner, James M and Silva, Rebeka and Yadav, Sumit and Bahney, Chelsea S and James, Aaron W and Kim, Reuben H and Klein, Ophir D and Hong, Christine},
title = {{p75\<sup\>NTR\</sup\> orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis}},
journal = {Science advances},
year = {2026},
month = oct,
volume = {12},
number = {43},
pages = {eaef7786},
publisher = {American Association for the Advancement of Science},
issn = {2375-2548},
doi = {10.1126/sciadv.aef7786},
url = {https://doi.org/10.1126/sciadv.aef7786},
pmid = {42905810},
pmcid = {PMC13685922}
}

RIS

TY - JOUR
AU - Kadota-Watanabe, Chiho
AU - Suh, Jinsook
AU - Yin, Eric
AU - Zhao, Byron
AU - Kim, Jey
AU - Zhang, Yan
AU - Chang, In-Won
AU - Ramesh, Sowmya
AU - Lee, Yuna
AU - Chen, Joshua
AU - Ahuja, Maulik
AU - Jahangiri, Sara
AU - Lao-Ngo, Isabelle
AU - Eisinger, Ursula
AU - Lindsey, Kate
AU - Zhang, Haihui
AU - Momen-Heravi, Fatemeh
AU - Du, Juan
AU - Gardner, James M
AU - Silva, Rebeka
AU - Yadav, Sumit
AU - Bahney, Chelsea S
AU - James, Aaron W
AU - Kim, Reuben H
AU - Klein, Ophir D
AU - Hong, Christine
TI - p75<sup>NTR</sup> orchestrates chondrogenesis and mechanoadaptation to preserve temporomandibular joint development and homeostasis
T2 - Science advances
J2 - Sci Adv
PY - 2026
DA - 2026/10/21
VL - 12
IS - 43
SP - eaef7786
SN - 2375-2548
PB - American Association for the Advancement of Science
DO - 10.1126/sciadv.aef7786
UR - https://doi.org/10.1126/sciadv.aef7786
LA - en
ER -

CSL-JSON

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