Tags

Type your tag names separated by a space and hit enter

Activation of cartilage matrix metalloproteinases by activated protein C.
Arthritis Rheum 2009; 60(3):780-91AR

Abstract

OBJECTIVE

To investigate the role of activated protein C (APC) in cartilage degradation.

METHODS

Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNFalpha), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay.

RESULTS

Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1alpha and TNFalpha stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1alpha-treated and TNFalpha-treated cartilage, but not in normal or in RetA-treated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity.

CONCLUSION

APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis.

Authors+Show Affiliations

University of Sydney at Royal North Shore Hospital, St. Leonards, New South Wales, Australia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19248107

Citation

Jackson, Miriam T., et al. "Activation of Cartilage Matrix Metalloproteinases By Activated Protein C." Arthritis and Rheumatism, vol. 60, no. 3, 2009, pp. 780-91.
Jackson MT, Smith MM, Smith SM, et al. Activation of cartilage matrix metalloproteinases by activated protein C. Arthritis Rheum. 2009;60(3):780-91.
Jackson, M. T., Smith, M. M., Smith, S. M., Jackson, C. J., Xue, M., & Little, C. B. (2009). Activation of cartilage matrix metalloproteinases by activated protein C. Arthritis and Rheumatism, 60(3), pp. 780-91. doi:10.1002/art.24303.
Jackson MT, et al. Activation of Cartilage Matrix Metalloproteinases By Activated Protein C. Arthritis Rheum. 2009;60(3):780-91. PubMed PMID: 19248107.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of cartilage matrix metalloproteinases by activated protein C. AU - Jackson,Miriam T, AU - Smith,Margaret M, AU - Smith,Susan M, AU - Jackson,Christopher J, AU - Xue,Meilang, AU - Little,Christopher B, PY - 2009/2/28/entrez PY - 2009/2/28/pubmed PY - 2009/4/28/medline SP - 780 EP - 91 JF - Arthritis and rheumatism JO - Arthritis Rheum. VL - 60 IS - 3 N2 - OBJECTIVE: To investigate the role of activated protein C (APC) in cartilage degradation. METHODS: Chondrocyte expression of protein C, endothelial protein C receptor (EPCR), and thrombomodulin (TM) were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). APC was immunolocalized in developing joints and in osteoarthritic (OA) cartilage from humans. The effect of APC on aggrecan and collagen degradation was examined in explant cultures of ovine cartilage in control cultures and in cultures stimulated with interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNFalpha), or retinoic acid (RetA), using colorimetric assays and Western blotting. Chondrocyte expression of matrix metalloproteinases (MMPs), ADAMTS, and tissue inhibitor of metalloproteinases (TIMPs) was measured by RT-PCR. MMP-2 and MMP-9 activity was evaluated by gelatin zymography and MMP-13 by fluorogenic assay. RESULTS: Positive cellular immunostaining for APC was found at sites of MMP activity in developing joints and in OA, but not normal, cartilage. Chondrocytes expressed messenger RNA for protein C, EPCR, and TM, with the latter 2 levels increased by IL-1alpha and TNFalpha stimulation. APC augmented aggrecan release and initiated collagen breakdown in IL-1alpha-treated and TNFalpha-treated cartilage, but not in normal or in RetA-treated cartilage. APC-stimulated aggrecan and collagen breakdown were due to MMP activity but were not associated with modulation of MMP, ADAMTS, or TIMP expression. APC resulted in MMP-13 activation in cartilage cultures. APC could not directly activate proMMP-13, but it was associated with increased MMP-2 and MMP-9 activity. CONCLUSION: APC may be a relevant activator of MMPs in cartilage and may play a role in progressive cartilage degradation in arthritis. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/19248107/Activation_of_cartilage_matrix_metalloproteinases_by_activated_protein_C_ L2 - https://doi.org/10.1002/art.24303 DB - PRIME DP - Unbound Medicine ER -