Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3- and 7D4) and collagen damage in cyclically load-injured articular cartilage

Peggy M. Lin, Chih Tung Christopher Chen, Peter A. Torzilli

Research output: Contribution to journalArticle

122 Citations (Scopus)

Abstract

Objective: To determine whether load-induced injury causes alterations in proteoglycan (PG), stromelysin-1 (MMP-3) and collagen in articular cartilage. Methods: Mature bovine cartilage was cyclically loaded at 0.5 Hz with 1 and 5 MPa for 1, 6 and 24 h. Immediately after loading explants were evaluated for cell viability. Alterations in matrix integrity were determined by measuring PG content, PG degradation using 7D4 and 3B3(-) antibodies, broken collagen using COL2-3/4m antibody, and stromelysin-1 content using a MMP-3 antibody. Results: Mechanical load caused cell death and PG loss starting from the articular surface and increasing in depth with loading time. There was a decrease in the 7D4 epitope (native chondroitin sulfate) in the superficial zone of cartilage loaded for longer than 1 h, but an increase around chondrocytes in the deep zone. The 3B3(-) staining for degraded/abnormal chondroitin-4-sulfate neoepitope appeared only in cartilage loaded under the most severe condition (5 MPa, 24 h). The elevation of stromelysin-1 was co-localized with broken collagen (COL2-3/4m) at the articular surface in explants loaded with 1 and 5 MPa for 24 h. Conclusions: Cell death and PG loss occurred within 6 h of cyclic loading. The elevation of MMP-3 following cell death was consistently found in the superficial zone of loaded cartilage. Since MMP-3 can degrade PG and super-activate procollagenase, the increase of MMP-3 can therefore induce matrix degradation and PG depletion in mechanically injured articular cartilage, both of which are important to the development of osteoarthritis.

Original languageEnglish (US)
Pages (from-to)485-496
Number of pages12
JournalOsteoarthritis and Cartilage
Volume12
Issue number6
DOIs
StatePublished - Jun 2004

Fingerprint

Matrix Metalloproteinase 3
Cartilage
Articular Cartilage
Proteoglycans
Matrix Metalloproteinases
Collagen
Degradation
Cell death
Antibodies
Cell Death
Chondroitin Sulfates
Joints
Epitopes
Chondrocytes
Osteoarthritis
Cell Survival
Cells
Staining and Labeling
Wounds and Injuries

Keywords

  • Cartilage
  • Cell death
  • Load-induced injury
  • Proteoglycan degradation
  • Stromelysin-1

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

Cite this

@article{8afd9b6626774367aba556007c091668,
title = "Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3- and 7D4) and collagen damage in cyclically load-injured articular cartilage",
abstract = "Objective: To determine whether load-induced injury causes alterations in proteoglycan (PG), stromelysin-1 (MMP-3) and collagen in articular cartilage. Methods: Mature bovine cartilage was cyclically loaded at 0.5 Hz with 1 and 5 MPa for 1, 6 and 24 h. Immediately after loading explants were evaluated for cell viability. Alterations in matrix integrity were determined by measuring PG content, PG degradation using 7D4 and 3B3(-) antibodies, broken collagen using COL2-3/4m antibody, and stromelysin-1 content using a MMP-3 antibody. Results: Mechanical load caused cell death and PG loss starting from the articular surface and increasing in depth with loading time. There was a decrease in the 7D4 epitope (native chondroitin sulfate) in the superficial zone of cartilage loaded for longer than 1 h, but an increase around chondrocytes in the deep zone. The 3B3(-) staining for degraded/abnormal chondroitin-4-sulfate neoepitope appeared only in cartilage loaded under the most severe condition (5 MPa, 24 h). The elevation of stromelysin-1 was co-localized with broken collagen (COL2-3/4m) at the articular surface in explants loaded with 1 and 5 MPa for 24 h. Conclusions: Cell death and PG loss occurred within 6 h of cyclic loading. The elevation of MMP-3 following cell death was consistently found in the superficial zone of loaded cartilage. Since MMP-3 can degrade PG and super-activate procollagenase, the increase of MMP-3 can therefore induce matrix degradation and PG depletion in mechanically injured articular cartilage, both of which are important to the development of osteoarthritis.",
keywords = "Cartilage, Cell death, Load-induced injury, Proteoglycan degradation, Stromelysin-1",
author = "Lin, {Peggy M.} and Chen, {Chih Tung Christopher} and Torzilli, {Peter A.}",
year = "2004",
month = "6",
doi = "10.1016/j.joca.2004.02.012",
language = "English (US)",
volume = "12",
pages = "485--496",
journal = "Osteoarthritis and Cartilage",
issn = "1063-4584",
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T1 - Increased stromelysin-1 (MMP-3), proteoglycan degradation (3B3- and 7D4) and collagen damage in cyclically load-injured articular cartilage

AU - Lin, Peggy M.

AU - Chen, Chih Tung Christopher

AU - Torzilli, Peter A.

PY - 2004/6

Y1 - 2004/6

N2 - Objective: To determine whether load-induced injury causes alterations in proteoglycan (PG), stromelysin-1 (MMP-3) and collagen in articular cartilage. Methods: Mature bovine cartilage was cyclically loaded at 0.5 Hz with 1 and 5 MPa for 1, 6 and 24 h. Immediately after loading explants were evaluated for cell viability. Alterations in matrix integrity were determined by measuring PG content, PG degradation using 7D4 and 3B3(-) antibodies, broken collagen using COL2-3/4m antibody, and stromelysin-1 content using a MMP-3 antibody. Results: Mechanical load caused cell death and PG loss starting from the articular surface and increasing in depth with loading time. There was a decrease in the 7D4 epitope (native chondroitin sulfate) in the superficial zone of cartilage loaded for longer than 1 h, but an increase around chondrocytes in the deep zone. The 3B3(-) staining for degraded/abnormal chondroitin-4-sulfate neoepitope appeared only in cartilage loaded under the most severe condition (5 MPa, 24 h). The elevation of stromelysin-1 was co-localized with broken collagen (COL2-3/4m) at the articular surface in explants loaded with 1 and 5 MPa for 24 h. Conclusions: Cell death and PG loss occurred within 6 h of cyclic loading. The elevation of MMP-3 following cell death was consistently found in the superficial zone of loaded cartilage. Since MMP-3 can degrade PG and super-activate procollagenase, the increase of MMP-3 can therefore induce matrix degradation and PG depletion in mechanically injured articular cartilage, both of which are important to the development of osteoarthritis.

AB - Objective: To determine whether load-induced injury causes alterations in proteoglycan (PG), stromelysin-1 (MMP-3) and collagen in articular cartilage. Methods: Mature bovine cartilage was cyclically loaded at 0.5 Hz with 1 and 5 MPa for 1, 6 and 24 h. Immediately after loading explants were evaluated for cell viability. Alterations in matrix integrity were determined by measuring PG content, PG degradation using 7D4 and 3B3(-) antibodies, broken collagen using COL2-3/4m antibody, and stromelysin-1 content using a MMP-3 antibody. Results: Mechanical load caused cell death and PG loss starting from the articular surface and increasing in depth with loading time. There was a decrease in the 7D4 epitope (native chondroitin sulfate) in the superficial zone of cartilage loaded for longer than 1 h, but an increase around chondrocytes in the deep zone. The 3B3(-) staining for degraded/abnormal chondroitin-4-sulfate neoepitope appeared only in cartilage loaded under the most severe condition (5 MPa, 24 h). The elevation of stromelysin-1 was co-localized with broken collagen (COL2-3/4m) at the articular surface in explants loaded with 1 and 5 MPa for 24 h. Conclusions: Cell death and PG loss occurred within 6 h of cyclic loading. The elevation of MMP-3 following cell death was consistently found in the superficial zone of loaded cartilage. Since MMP-3 can degrade PG and super-activate procollagenase, the increase of MMP-3 can therefore induce matrix degradation and PG depletion in mechanically injured articular cartilage, both of which are important to the development of osteoarthritis.

KW - Cartilage

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KW - Proteoglycan degradation

KW - Stromelysin-1

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