Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis

Tsuchiya, Akiho; Yano, Masato; Tocharus, Jiraporn; Kojima, Hisae; Fukumoto, Manabu; Kawaichi, Masashi; Oka, Chio

doi:10.1016/j.bone.2005.03.015

Cited by 126 publications

(122 citation statements)

References 33 publications

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“…HtrA1 levels are also increased in both OA and RA synovial fluids, and synovial fibroblasts secrete HtrA1 (99). Furthermore, levels of both HtrA1 and HtrA3 are elevated in experimental arthritis (100,101).…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

“…HtrA1 is expressed by hypertrophic chondrocytes in both normal and pathologic situations. During bone formation, HtrA1 is expressed by hypertrophic chondrocytes, and this may be important in inhibiting local TGF␤ signaling and allowing chondrocyte differentiation (101). HtrA1 is also increased in the setting of CIA, where resting chondrocytes proceed to terminal hypertrophy (101).…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

“…During bone formation, HtrA1 is expressed by hypertrophic chondrocytes, and this may be important in inhibiting local TGF␤ signaling and allowing chondrocyte differentiation (101). HtrA1 is also increased in the setting of CIA, where resting chondrocytes proceed to terminal hypertrophy (101). In the normal adult joint, TGF␤ proteins are important in maintaining a layer of articular cartilage by preventing chondrocyte differentiation and hypertrophy and stimulating the synthesis of proteoglycans and collagens (103,104).…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

“…In the normal adult joint, TGF␤ proteins are important in maintaining a layer of articular cartilage by preventing chondrocyte differentiation and hypertrophy and stimulating the synthesis of proteoglycans and collagens (103,104). Overexpression of HtrA1 may promote arthritis by inhibiting TGF␤ and accelerating chondrocyte hypertrophic differentiation (101). Furthermore, HtrA1 can digest biglycan, decorin, aggrecan, fibromodulin, fibronectin, and matrix Gla protein and thus promote cartilage ECM degradation (99)(100)(101)105).…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

“…Overexpression of HtrA1 may promote arthritis by inhibiting TGF␤ and accelerating chondrocyte hypertrophic differentiation (101). Furthermore, HtrA1 can digest biglycan, decorin, aggrecan, fibromodulin, fibronectin, and matrix Gla protein and thus promote cartilage ECM degradation (99)(100)(101)105). HtrA3 can also degrade biglycan and decorin (100).…”

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

See 4 more Smart Citations

Emerging roles of serine proteinases in tissue turnover in arthritis

Milner

Patel

Rowan

2008

Arthritis & Rheumatism

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Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

Section: High-temperature Requirement Proteinasesmentioning

confidence: 99%

See 3 more Smart Citations

Emerging roles of serine proteinases in tissue turnover in arthritis

Milner

Patel

Rowan

2008

Arthritis & Rheumatism

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Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Sato

Konomi

Yamasaki

et al. 2006

Arthritis & Rheumatism

154

130

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Objective. To analyze the differences in gene expression profiles of chondrocytes in intact and damaged regions of cartilage from the same knee joint of patients with osteoarthritis (OA) of the knee.Methods. We compared messenger RNA expression profiles in regions of intact and damaged cartilage (classified according to the Mankin scale) obtained from patients with knee OA. Five pairs of intact and damaged regions of OA cartilage were evaluated by oligonucleotide array analysis using a double in vitro transcription amplification technique. The microarray data were confirmed by real-time quantitative polymerase chain reaction (PCR) amplification and were compared with previously published data.Results. About 1,500 transcripts, which corresponded to 8% of the expressed transcripts, showed >2-fold differences in expression between the cartilage tissue pairs. Approximately 10% of these transcripts (n ‫؍‬ 151) were commonly expressed in the 5 patient samples. Accordingly, 114 genes (35 genes expressed in intact > damaged; 79 genes expressed in intact < damaged) were selected. The expression of some genes related to the wound-healing process, including cell proliferation and interstitial collagen synthesis, was higher in damaged regions than in intact regions, similar to the findings for genes that inhibit matrix degradation. Comparisons of the real-time quantitative PCR data with the previously reported data support the validity of our microarray data.Conclusion. Differences between intact and damaged regions of OA cartilage exhibited a similar pattern among the 5 patients examined, indicating the presence of common mechanisms that contribute to cartilage destruction. Elucidation of this mechanism is important for the development of effective treatments for OA.

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Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis

Wu¹,

Liu²,

Bemis³

et al. 2007

Arthritis & Rheumatism

152

112

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Objective. To identify potential molecular mediators and biomarkers for osteoarthritis (OA), through comparative proteomic analysis of articular cartilage tissue obtained from normal donors without OA (n ‫؍‬ 7) and patients with OA (n ‫؍‬ 7).Methods. The proteomic analyses comprised extraction of soluble proteins from cartilage, separation of the protein mixtures by sodium dodecyl sulfatepolyacrylamide gel electrophoresis followed by in-gel digestion, and subsequent nano-liquid chromatographytandem mass spectrometry analysis in conjunction with a database search for protein identification and semiquantitation.Results. A total of 814 distinct proteins were identified with high confidence from 14 samples; 420 of these proteins were detected with >3 unique peptides in at least 4 samples from the same group. Using stringent criteria, 59 proteins were found to be differentially expressed in OA cartilage. Gene Ontology and Ingenuity pathway analysis tools were used to characterize these proteins into functional categories. One of the upregulated proteins, HtrA1, a serine protease, was detected at high levels in cartilage.Conclusion. Altered protein expression in the disease state is associated with many aspects of the pathogenesis of OA, such as increased proteolysis, lipid metabolism, immune response, and decreased signal transduction. To our knowledge, this is the first time that a large portion of these proteins and their expression patterns were identified in cartilage, thus providing new insights for finding novel pathologic mediators and biomarkers of OA.

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Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis

Cited by 126 publications

References 33 publications

Emerging roles of serine proteinases in tissue turnover in arthritis

Emerging roles of serine proteinases in tissue turnover in arthritis

Comparative analysis of gene expression profiles in intact and damaged regions of human osteoarthritic cartilage

Comparative proteomic characterization of articular cartilage tissue from normal donors and patients with osteoarthritis

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