Structural and functional analysis of intra-articular interzone tissue in axolotl salamanders

R. S. Cosden-Decker, M. M. Bickett, C. Lattermann, J. N. MacLeod

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Objective: Knowledge of mechanisms directing diarthrodial joint development may be useful in understanding joint pathologies and identifying new therapies. We have previously established that axolotl salamanders can fully repair large articular cartilage lesions, which may be due to the presence of an interzone-like tissue in the intra-articular space. Study objectives were to further characterize axolotl diarthrodial joint structure and determine the differentiation potential of interzone-like tissue in a skeletal microenvironment. Design: Diarthrodial joint morphology and expression of aggrecan, brother of CDO (BOC), type I collagen, type II collagen, and growth/differentiation factor 5 (GDF5) were examined in femorotibial joints of sexually mature (>12 months) axolotls. Joint tissue cellularity was evaluated in individuals from 2 to 24 months of age. Chondrogenic potential of the interzone was evaluated by placing interzone-like tissue into 4 mm tibial defects. Results: Cavitation reached completion in the femoroacetabular and humeroradial joints, but an interzone-like tissue was retained in the intra-articular space of distal limb joints. Joint tissue cellularity decreased to 7 months of age and then remained stable. Gene expression patterns of joint markers are broadly similar in developing mammals and mature axolotls. When interzone-like tissue was transplanted into critical size skeletal defects, an accessory joint developed within the defect site. Conclusions: These experiments indicate that mature axolotl diarthrodial joints are phenotypically similar to developing synovial joints in mammals. Generation of an accessory joint by interzone-like tissue suggests multipotent cellular differentiation potential similar to that of interzone cells in the mammalian fetus. The data support the axolotl as a novel vertebrate model for joint development and repair.

Original languageEnglish
Pages (from-to)1347-1356
Number of pages10
JournalOsteoarthritis and Cartilage
Issue number11
StatePublished - Nov 2012

Bibliographical note

Funding Information:
Financial support was received from the Kentucky Equine Drug Research Council , the Lourie Foundation , the Gluck Equine Research Center , and the University of Kentucky Department of Orthopaedic Surgery . Dr Christian Lattermann is currently supported by a University of Kentucky Physician Scientist Development Award and by an NIH-NIAMS K-23 AR060275-01A1 . These study sponsors were not involved in the study design, data collection or analysis; or in the writing of the manuscript. Furthermore, they did not affect the decision to submit the manuscript for publication.


  • Amphibian
  • Articular cartilage repair
  • Axolotl salamander
  • Joint development
  • Joint interzone

ASJC Scopus subject areas

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine


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