Cargando…
Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs
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 tis...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212078/ https://www.ncbi.nlm.nih.gov/pubmed/35608281 http://dx.doi.org/10.1242/bio.059381 |
_version_ | 1784730502258753536 |
---|---|
author | Kim, Minwook Koyama, Eiki Saunders, Cheri M. Querido, William Pleshko, Nancy Pacifici, Maurizio |
author_facet | Kim, Minwook Koyama, Eiki Saunders, Cheri M. Querido, William Pleshko, Nancy Pacifici, Maurizio |
author_sort | Kim, Minwook |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9212078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92120782022-06-22 Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs Kim, Minwook Koyama, Eiki Saunders, Cheri M. Querido, William Pleshko, Nancy Pacifici, Maurizio Biol Open Research Article 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. The Company of Biologists Ltd 2022-06-15 /pmc/articles/PMC9212078/ /pubmed/35608281 http://dx.doi.org/10.1242/bio.059381 Text en © 2022. Published by The Company of Biologists Ltd https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Kim, Minwook Koyama, Eiki Saunders, Cheri M. Querido, William Pleshko, Nancy Pacifici, Maurizio Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title | Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title_full | Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title_fullStr | Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title_full_unstemmed | Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title_short | Synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
title_sort | synovial joint cavitation initiates with microcavities in interzone and is coupled to skeletal flexion and elongation in developing mouse embryo limbs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212078/ https://www.ncbi.nlm.nih.gov/pubmed/35608281 http://dx.doi.org/10.1242/bio.059381 |
work_keys_str_mv | AT kimminwook synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs AT koyamaeiki synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs AT saunderscherim synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs AT queridowilliam synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs AT pleshkonancy synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs AT pacificimaurizio synovialjointcavitationinitiateswithmicrocavitiesininterzoneandiscoupledtoskeletalflexionandelongationindevelopingmouseembryolimbs |