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Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

ABSTRACT: Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

SUBMITTER: Iwamoto M

PROVIDER: S-EPMC2104487 | biostudies-literature | 2007 May

REPOSITORIES: biostudies-literature

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Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

Iwamoto Masahiro M Tamamura Yoshihiro Y Koyama Eiki E Komori Toshihisa T Takeshita Nobuo N Williams Julie A JA Nakamura Takashi T Enomoto-Iwamoto Motomi M Pacifici Maurizio M

Developmental biology 20070207 1

Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF- ...[more]

PMID: 17336282

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Project description:BackgroundThe use of particulated articular cartilage for repairing cartilage defects has been well established, but its use is currently limited by the availability and short shelf life of donor cartilage. Vitrification is an ice-free cryopreservation technology at ultralow temperatures for tissue banking. An optimized vitrification protocol has been developed for particulated articular cartilage; however, the equivalency of the long-term clinical efficacy of vitrified particulated articular cartilage compared with fresh articular cartilage has not yet been determined.HypothesisThe repair effect of vitrified particulated cartilage from pigs would be equivalent to or better than that of fresh particulated cartilage stored at 4°C for 21 days.Study designControlled laboratory study.MethodsA total of 19 pigs were randomly divided into 3 experimental groups: fresh particulated cartilage group (n = 8), vitrified particulated cartilage group (n = 8), and negative control group (no particulated cartilage in the defect; n = 3). An additional pig was used as the initial cartilage donor for the first set of surgical procedures. Pigs were euthanized after 6 months to obtain femoral condyles, and the contralateral condyle was used as the positive (no defect) control. Samples were evaluated for gross morphology using the Outerbridge and Osteoarthritis Research Society International (OARSI) scoring systems, histology (safranin O, collagen type I/II, DAPI), and chondrocyte viability using live-dead membrane integrity staining.ResultsThere were no infections after surgery, and all 19 pigs were followed for the duration of the study. The OARSI grades for the fresh and vitrified particulated cartilage groups were 2.44 ± 1.35 and 2.00 ± 0.80, respectively, while the negative control group was graded significantly higher at 4.83 ± 0.29. Analysis of histological and fluorescent staining demonstrated that the fresh and vitrified particulated cartilage groups had equivalent regeneration within cartilage defects, with similar cell viability and densities and expression of proteoglycans and collagen type I/II.ConclusionThe implantation of fresh or vitrified particulated cartilage resulted in the equivalent repair of focal cartilage defects when evaluated at 6 months after surgery.Clinical relevanceThe vitrification of particulated cartilage is a viable option for long-term storage for cartilage tissue banking and could greatly increase the availability of donor tissue for transplantation.

Dataset Information

Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

Publications

Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

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