ArticleBiology open2022
Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs.
Article in Biology open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Motion as Medicine: Physical Activity, Joint Sensitivity, and Pain Management-A Narrative Review.Medical sciences (Basel, Switzerland) · 2026Review
- Article
- Synovial joint cavitation during limb skeletogenesis entails Na/K-ATPase ion pump expression and osmoregulatory activity.Development (Cambridge, England) · 2025Article
- Genetic Deficiency of Hyaluronan Synthase 2 in the Developing Limb Mesenchyme Impairs Postnatal Synovial Joint Formation.Biomedicines · 2025Article
- PDGFRα signaling regulates cartilage and fibrous tissue differentiation during synovial joint development.Nature communications · 2025Article
- Synovial joints were present in the common ancestor of jawed fish but lacking in jawless fish.PLoS biology · 2025Article
- The methylomic landscape of human articular cartilage development contains epigenetic signatures of osteoarthritis risk.American journal of human genetics · 2024Article
- Comparison of knee joint and temporomandibular joint development in pig embryos.Animal biotechnology · 2024Article
- A tutorial on optical photothermal infrared (O-PTIR) microscopy.APL photonics · 2024Article
- Synergistic effects of biological stimuli and flexion induce microcavities promote hypertrophy and inhibit chondrogenesis during in vitro culture of human mesenchymal stem cell aggregates.Biotechnology journal · 2024Article
- Reduction in postnatal weight-bearing does not alter the trajectory of murine meniscus growth and maturation.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2024Article
- Lack of skeletal muscle contraction disrupts fibrous tissue morphogenesis in the developing murine knee.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023Article
- Rapid specialization and stiffening of the primitive matrix in developing articular cartilage and meniscus.Acta biomaterialia · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The synovial cavity and its fluid are essential for joint function and lubrication, but their developmental biology remains largely obscure. Here, we analyzed E12.5 to E18.5 mouse embryo hindlimbs and discovered that cavitation initiates around E15.0 with emergence of multiple, discrete, µm-wide tissue discontinuities we term microcavities in interzone, evolving into a single joint-wide cavity within 12 h in knees and within 72-84 h in interphalangeal joints. The microcavities were circumscribed by cells as revealed by mTmG imaging and exhibited a carbohydrate and protein content based on infrared spectral imaging at micro and nanoscale. Accounting for differing cavitation kinetics, we found that the growing femur and tibia anlagen progressively flexed at the knee over time, with peak angulation around E15.5 exactly when the full knee cavity consolidated; however, interphalangeal joint geometry changed minimally over time. Indeed, cavitating knee interzone cells were elongated along the flexion angle axis and displayed oblong nuclei, but these traits were marginal in interphalangeal cells. Conditional Gdf5Cre-driven ablation of Has2 - responsible for production of the joint fluid component hyaluronic acid (HA) - delayed the cavitation process. Our data reveal that cavitation is a stepwise process, brought about by sequential action of microcavities, skeletal flexion and elongation, and HA accumulation. This article has an associated First Person interview with the first author of the paper.
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Registered trials
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