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Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability.

Publication ,  Journal Article
Ding, L; Zampogna, B; Vasta, S; Jang, KW; De Caro, F; Martin, JA; Amendola, A
Published in: Am J Sports Med
October 2015

BACKGROUND: Transplantation of osteochondral allografts (OCAs) freshly preserved for ≥30 days has proven to be a reliable technique for cartilage resurfacing. However, the prolonged storage of allografts comes at the expense of chondrocyte viability, which declines precipitously after 14 days under refrigeration. Despite this, radiographic data indicate that most allograft cartilage remains stable for years after implantation. The apparent durability of partially devitalized cartilage begs the question of how the extracellular matrix is maintained. HYPOTHESIS: Compared with patients' defect cartilage, replacement OCAs freshly preserved for 36 days on average contain significantly lower levels of cartilage matrix-destructive metalloproteinases, which may contribute to the long-term stability of implanted grafts. STUDY DESIGN: Descriptive laboratory study. METHODS: Chondrocyte density was determined by the cell yield from digested cartilage and by double-strand DNA content quantified with PicoGreen assay. Chondrocyte viability was estimated by staining enzymatically isolated chondrocytes with calcein AM and ethidium homodimer-2. Cartilage proteoglycan (PG) content was analyzed with dimethylmethylene blue assay. The in vitro 48-hour release of PG-depleting metalloproteinases including matrix metalloproteinase (MMP)-1, -3, -13, and ADAMTS-5 from cartilage was examined with Western blotting. The data were compared between diseased cartilage from patients and samples from matched grafts. The relative amount of MMP-3 to its endogenous inhibitor, tissue inhibitor of MMP-1 (TIMP-1), was also determined with Western blotting. RESULTS: Chondrocyte density decreased linearly with allograft storage time and declined by an average of 43%. PG content decreased while the percentage of nonviable chondrocytes increased with storage time, with the former showing less linearity. However, PG content remained in the normal range and was significantly higher than that in patients' defect cartilage. Correspondingly, significantly less PG-depleting metalloproteinases and a much lower MMP-3/TIMP-1 ratio were detected in allograft cartilage than in patients' diseased cartilage. CONCLUSION: These findings indicated that, at the time of implantation, fresh-preserved OCAs contained significantly lower levels of PG-depleting metalloproteinases compared with patients' defect cartilage, which might contribute to their long-term stability in vivo. CLINICAL RELEVANCE: The comparatively low expression of cartilage-dissolving metalloproteinases in human OCAs freshly preserved over 30 days offers support to the long-term durability of implanted grafts. Based on study data that showed similarity in the response to inflammatory cytokines between patients' cartilage and OCA cartilage, strategies that can alleviate inflammation may provide extra benefit for the survival of implanted grafts. In terms of the practice of graft preservation, agents that can keep balance between the ATP supply and demand or stabilize the cell membrane or inhibit the activation of metalloproteinases may significantly improve cell viability in fresh-preserved OCAs with a storage time longer than 5 weeks.

Duke Scholars

Published In

Am J Sports Med

DOI

EISSN

1552-3365

Publication Date

October 2015

Volume

43

Issue

10

Start / End Page

2459 / 2468

Location

United States

Related Subject Headings

  • Young Adult
  • Tissue Preservation
  • Proteoglycans
  • Orthopedics
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1
  • Male
  • Humans
  • Graft Survival
  • Female
 

Citation

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Chicago
ICMJE
MLA
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Ding, L., Zampogna, B., Vasta, S., Jang, K. W., De Caro, F., Martin, J. A., & Amendola, A. (2015). Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability. Am J Sports Med, 43(10), 2459–2468. https://doi.org/10.1177/0363546515596407
Ding, Lei, Biagio Zampogna, Sebastiano Vasta, Kee Woong Jang, Francesca De Caro, James A. Martin, and Annunziato Amendola. “Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability.Am J Sports Med 43, no. 10 (October 2015): 2459–68. https://doi.org/10.1177/0363546515596407.
Ding L, Zampogna B, Vasta S, Jang KW, De Caro F, Martin JA, et al. Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability. Am J Sports Med. 2015 Oct;43(10):2459–68.
Ding, Lei, et al. “Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability.Am J Sports Med, vol. 43, no. 10, Oct. 2015, pp. 2459–68. Pubmed, doi:10.1177/0363546515596407.
Ding L, Zampogna B, Vasta S, Jang KW, De Caro F, Martin JA, Amendola A. Why Do Osteochondral Allografts Survive? Comparative Analysis of Cartilage Biochemical Properties Unveils a Molecular Basis for Durability. Am J Sports Med. 2015 Oct;43(10):2459–2468.
Journal cover image

Published In

Am J Sports Med

DOI

EISSN

1552-3365

Publication Date

October 2015

Volume

43

Issue

10

Start / End Page

2459 / 2468

Location

United States

Related Subject Headings

  • Young Adult
  • Tissue Preservation
  • Proteoglycans
  • Orthopedics
  • Matrix Metalloproteinase 3
  • Matrix Metalloproteinase 1
  • Male
  • Humans
  • Graft Survival
  • Female