Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage

Kazushi Imai, Satoru Ohta, Tadami Matsumoto, Noboru Fujimoto, Hiroshi Sato, Motoharu Seiki, Yasunori Okada

Research output: Contribution to journalArticle

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Abstract

Matrix metalloproteinases (MMPs) are expressed in osteoarthritic (OA) cartilage and are thought to be involved in the degradation of cartilage extracellular matrix (ECM). Among these proteinases, MMP-2 (gelatinase A) demonstrates a wide range of substrate specificity against the ECM present in cartilage. Although MMP-2 expression increases in OA cartilage, the activation mechanism of the corresponding zymogen (pro-MMP-2) in cartilage is unknown. In this study, we examined the expression pattern of membrane-type 1 MMP (MT1-MMP) in human OA articular cartilage and its correlation with the activation of pro-MMP-2. Immunohistochemical studies demonstrate that MT1- MMP localizes to the chondrocytes in the superficial and transitional zones in all of the samples examined directly correlating with cartilage degradation. Reverse transcription polymerase chain reaction confirmed the predominant expression of MT1-MMP mRNA in the OA cartilage. In situ hybridization revealed the site of expression of MT1-MMP in OA cartilage to be the chondrocytes. Through gelatin zymography and a sandwich enzyme immunoassay it was demonstrated that OA cartilage explants secrete significantly higher levels of pro-MMP-2 than normal samples. Pro-MMP-2 activation was enhanced in the OA cartilage samples and correlated with MT1- MMP expression in the cartilage. Plasma membranes prepared from cultured chondrocytes with MT1-MMP expression and those directly isolated from OA cartilage could activate pro-MMP-2. MT1-MMP gene expression in cultured chondrocytes was induced by treatment with interleukin-1 α and/or tumor necrosis factor-α. These data suggest that cytokine-induced MT1-MMP in the chondrocytes may play a key role in the activation of pro-MMP-2 in the OA articular cartilage, leading to cartilage destruction through ECM degradation.

Original languageEnglish
Pages (from-to)245-256
Number of pages12
JournalAmerican Journal of Pathology
Volume151
Issue number1
Publication statusPublished - 1997

Fingerprint

Matrix Metalloproteinase 14
Cartilage
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Chondrocytes
Membranes
Extracellular Matrix
Articular Cartilage
progelatinase
Enzyme Precursors
Gelatin
Substrate Specificity
Immunoenzyme Techniques
Interleukin-1
Reverse Transcription
In Situ Hybridization

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Imai, K., Ohta, S., Matsumoto, T., Fujimoto, N., Sato, H., Seiki, M., & Okada, Y. (1997). Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage. American Journal of Pathology, 151(1), 245-256.

Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage. / Imai, Kazushi; Ohta, Satoru; Matsumoto, Tadami; Fujimoto, Noboru; Sato, Hiroshi; Seiki, Motoharu; Okada, Yasunori.

In: American Journal of Pathology, Vol. 151, No. 1, 1997, p. 245-256.

Research output: Contribution to journalArticle

Imai, K, Ohta, S, Matsumoto, T, Fujimoto, N, Sato, H, Seiki, M & Okada, Y 1997, 'Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage', American Journal of Pathology, vol. 151, no. 1, pp. 245-256.
Imai, Kazushi ; Ohta, Satoru ; Matsumoto, Tadami ; Fujimoto, Noboru ; Sato, Hiroshi ; Seiki, Motoharu ; Okada, Yasunori. / Expression of membrane-type 1 matrix metalloproteinase and activation of progelatinase A in human osteoarthritic cartilage. In: American Journal of Pathology. 1997 ; Vol. 151, No. 1. pp. 245-256.
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