ArticleCell2020
Evolutionary Selection and Constraint on Human Knee Chondrocyte Regulation Impacts Osteoarthritis Risk.
Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 2 of them syntheses that pooled it.
What it found
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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.
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Who cites it
78 citing papers in PubMed, 2 syntheses or guidelines pooled it, 160 citations in OpenAlex.
- Prevalence of knee osteoarthritis in the Chinese population, 2013-2023: a systematic review and meta-analysis.Journal of orthopaedic surgery and research · 2025Pooled it
- Association between growth differentiation factor 5 rs143383 genetic polymorphism and the risk of knee osteoarthritis among Caucasian but not Asian: a meta-analysis.Arthritis research & therapy · 2020Pooled it
- The gene-regulatory evolution of the human skeleton.Nature · 2026Article
- Article
- A Human Accelerated Region Drives Opposing Heterochronic Changes in Craniofacial and Limb Development.bioRxiv : the preprint server for biology · 2026Article
- Segmentally Duplicated Regulatory Elements Undergo Human-Specific Rewiring.Molecular biology and evolution · 2026Article
- Dissecting the genetic architecture of knee alignment reveals its contribution to osteoarthritis risk.medRxiv : the preprint server for health sciences · 2026Article
- Nanozyme hydrogels remodel pathological microenvironment for temporomandibular joint osteoarthritis therapy via inhibiting MAPK signal pathway.Bioactive materials · 2026Article
- Modular genetic architecture underlies human hand and foot evolution.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- miR-205a mediated suppression of CDH11 disrupts Wnt/β-catenin signaling and impairs chondrocyte differentiation.Cell death discovery · 2026Article
- In Vitro Massively Parallel Screening of Human Regulatory Elements Involved in Postcranial Skeletal Development for Differential Activity Compared to Chimpanzee.Genome biology and evolution · 2026Article
- Cross-species prediction reveals chromatin regions with increased accessibility in humans.Science advances · 2026Article
- Identification of a putative progenitor-like chondrocyte subpopulation in osteoarthritic human cartilage.Stem cell research & therapy · 2026Article
- Profiling the epigenomic landscape of late embryonic and adult mouse hind limb muscles.Scientific reports · 2026Article
- Patient Perception of Lower-Limb Straightness at One Week After Unrestricted Kinematically Aligned Total Knee Arthroplasty: Exploring the Concept of "Inherent Straightness".Journal of personalized medicine · 2026Article
- Segmentally duplicated regulatory elements undergo human-specific rewiring.bioRxiv : the preprint server for biology · 2025Article
- A curated dataset of great ape genome diversity.Scientific data · 2025Article
- A combined genomic arrhythmia propensity score delineates cumulative risk.Cell reports. Medicine · 2025Article
- The roles of TGF-β, Wnt, and MAPK signaling pathways in joint lineage specification in vitro and ex vivo.Stem cell reports · 2025Article
- Complex Regulatory Interactions at GDF5 Shape Joint Morphology and Osteoarthritis Disease Risk.Arthritis & rheumatology (Hoboken, N.J.) · 2025Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
Abstract
During human evolution, the knee adapted to the biomechanical demands of bipedalism by altering chondrocyte developmental programs. This adaptive process was likely not without deleterious consequences to health. Today, osteoarthritis occurs in 250 million people, with risk variants enriched in non-coding sequences near chondrocyte genes, loci that likely became optimized during knee evolution. We explore this relationship by epigenetically profiling joint chondrocytes, revealing ancient selection and recent constraint and drift on knee regulatory elements, which also overlap osteoarthritis variants that contribute to disease heritability by tending to modify constrained functional sequence. We propose a model whereby genetic violations to regulatory constraint, tolerated during knee development, lead to adult pathology. In support, we discover a causal enhancer variant (rs6060369) present in billions of people at a risk locus (GDF5-UQCC1), showing how it impacts mouse knee-shape and osteoarthritis. Overall, our methods link an evolutionarily novel aspect of human anatomy to its pathogenesis.
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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.