Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs

Minwook Kim, Eiki Koyama, Cheri M. Saunders, William Querido, Nancy Pleshko, Maurizio Pacifici

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

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.

Original languageEnglish (US)
Article numberbio059381
JournalBiology Open
Volume11
Issue number6
DOIs
StatePublished - Jun 2022
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology
  • General Agricultural and Biological Sciences

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