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Published on: March 18, 2022
Expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic cartilage
Satoko Naito1, Takayuki Shiomi, Aiko Okada
1Department of Pathology, School of Medicine, Keio University, Tokyo.
Abstract:
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)1, 4, 5, 8, 9 and 15, members of the ADAMTS gene family, have the ability to degrade a major cartilage proteoglycan, aggrecan, at the specific sites, and thus are called 'aggrecanases'. The expression of these ADAMTS species was examined in human osteoarthritic articular cartilage on reverse transcription-polymerase chain reaction. The results demonstrated the predominant expression of ADAMTS4 in osteoarthritic cartilage, while ADAMTS5 was constitutively expressed in osteoarthritic and normal cartilage. ADAMTS9 was expressed mainly in normal cartilage, whereas no or negligible expression of ADAMTS1, 8 and 15 was observed in either osteoarthritic or normal cartilage. In situ hybridization for ADAMTS4 indicated that chondrocytes in osteoarthritic cartilage expressed the mRNA. Two monoclonal antibodies to ADAMTS4 were developed, and immunolocalized ADAMTS4 to chondrocytes in the proteoglycan-depleted zones of osteoarthritic cartilage, showing a direct correlation with the Mankin scores. Immunoblotting indicated a major protein band of 58 kDa in the chondrocyte culture media and osteoarthritic cartilage tissue homogenates. These data demonstrate that among the six ADAMTS species, ADAMTS4 is mainly expressed in an active form in osteoarthritic cartilage, and suggest that ADAMTS4 may play an important role in the degradation of aggrecan in human osteoarthritic cartilage.
Insights
Aggrecanases, a group of enzymes including ADAMTS4, are involved in cartilage degradation. This study found ADAMTS4 is predominantly expressed in human osteoarthritic cartilage, suggesting its key role in aggrecan breakdown.
Area of Science:
- Biochemistry
- Molecular Biology
- Orthopedics
Background:
- Members of the ADAMTS (A disintegrin and metalloproteinase with thrombospondin motifs) gene family, specifically ADAMTS1, 4, 5, 8, 9, and 15, are known as aggrecanases.
- These enzymes degrade aggrecan, a major cartilage proteoglycan, at specific sites.
Purpose of the Study:
- To examine the expression of ADAMTS aggrecanases in human osteoarthritic articular cartilage.
- To investigate the role of ADAMTS4 in aggrecan degradation in osteoarthritis.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) to analyze ADAMTS gene expression.
- In situ hybridization to localize ADAMTS4 mRNA in cartilage.
- Development of monoclonal antibodies for immunolocalization of ADAMTS4.
- Immunoblotting to detect ADAMTS4 protein levels.
Main Results:
- ADAMTS4 was predominantly expressed in osteoarthritic cartilage, while ADAMTS5 was found in both normal and osteoarthritic cartilage.
- ADAMTS9 expression was higher in normal cartilage; ADAMTS1, 8, and 15 showed negligible expression.
- ADAMTS4 mRNA was localized to chondrocytes in osteoarthritic cartilage.
- Immunolocalization confirmed ADAMTS4 in chondrocytes within proteoglycan-depleted areas, correlating with Mankin scores.
Conclusions:
- ADAMTS4 is mainly expressed in an active form in human osteoarthritic cartilage.
- ADAMTS4 likely plays a significant role in the degradation of aggrecan in osteoarthritis.
- Further research into ADAMTS4 could lead to novel therapeutic strategies for osteoarthritis.
