Expression of bone morphogenetic proteins, receptors, and tissue inhibitors in human fetal, adult, and osteoarthritic articular cartilage

Chen, Andrew L.; Fang, Carrie; Liu, Chuanju; Leslie, Michael; Chang, Eric Y.; Cesare, Paul E. Di

doi:10.1016/j.orthres.2004.02.013

Cited by 50 publications

(56 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Human meniscus, bone, cartilage, synovium, ligament, tendon, fat, and skeletal muscle obtained from four normal human knees (provided by the Musculoskeletal Transplant Foundation, Edison, NJ) were frozen immediately after isolation and ground under liquid nitrogen (44). Total RNA was extracted by the acid-guanidium thiocyanate-phenol-chloroform single-step method followed by RNAeasy kit (Qiagen, Valencia, CA).…”

Section: Rna Preparation and Reverse Transcription Pcrmentioning

confidence: 99%

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Liu¹,

et al. 2006

Self Cite

View full text Add to dashboard Cite

Degradative fragments of cartilage oligomeric matrix protein (COMP) have been observed in arthritic patients. The physiological enzyme(s) that degrade COMP, however, remain unknown. We performed a yeast two-hybrid screen (Y2H) to search for proteins that associate with COMP to identify an interaction partner that might degrade it. One screen using the epidermal growth factor (EGF) domain of COMP as bait led to the discovery of ADAMTS-7. Rat ADAMTS-7 is composed of 1595 amino acids, and this protein exhibits higher expression in the musculoskeletal tissues. COMP binds directly to ADAMTS-7 in vitro and in native articular cartilage. ADAMTS-7 selectively interacts with the EGF repeat domain but not with the other three functional domains of COMP, whereas the four C-terminal TSP motifs of ADAMTS-7 are required and sufficient for association with COMP. The recombinant catalytic domain and intact ADAMTS-7 are capable of digesting COMP in vitro. The enzymatic activity of ADAMTS-7 requires the presence of Zn 2+ and appropriate pH (7.5-9.5), and the concentration of ADAMTS-7 in cartilage and synovium of patients with rheumatoid arthritis is significantly increased as compared to normal cartilage and synovium. ADAMTS-7 is the first metalloproteinase found to bind directly to and degrade COMP.-Liu, C., Kong, W., Ilalov, K., Yu, S., Xu, K., Prazak, L., Fajardo, M., Sehgal, B., Di Cesare, P. E. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. The extracellular matrix (ECM) of cartilage consists of several types of collagens, proteoglycans, and other noncollagenous macromolecules, all of which interact to form a highly specialized connective tissue (1). Early extracellular cartilage matrix degeneration in arthritis is the result of the action of degradative enzymes. As the severity of arthritis progresses, the synthesis and secretion of matrix-degrading enzymes markedly increase (2). The control 1 These authors contributed equally to this work.

show abstract

Section: Rna Preparation and Reverse Transcription Pcrmentioning

confidence: 99%

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Liu¹,

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…The primers for BMP-7 (276 bp) were: forward CAG CCT GCA AGA TAG CCA TT, and reverse GAG CAG GAA GAG ATC CGA TT (19). …”

Section: Quantitative Real-time Rt-pcrmentioning

confidence: 99%

Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma

Bašić‐Jukić¹,

Hudolin²,

Radic-Antolic³

et al. 2010

View full text Add to dashboard Cite

2 ABSTRACTRecent studies demonstrated that the expression pattern of bone morphogenetic protein 7(BMP-7) is altered in different tumors. We determined expression of BMP-7 in human clear cell renal carcinoma (CCRC).Samples from cancer and corresponding healthy tissue were obtained from 20 patients who underwent nephrectomy for CCRC. Expression of BMP-7 mRNA was determined by RT-PCR and protein expression was analyzed by immunohistochemistry.RT-PCR showed strong downregulation of BMP-7 mRNA in cancer tissue.

show abstract

“…Transcription PCR-Human meniscus, bone, cartilage, synovium, ligament, tendon, fat, and skeletal muscle obtained from four normal human knees (provided by the Musculoskeletal Transplant Foundation, Edison, NJ), were frozen immediately after isolation and ground under liquid nitrogen (41). Total RNA was extracted by the acid-guanidium thiocyanate-phenol-chloroform single-step method followed by RNAeasy kit (Qiagen, Valencia, CA).…”

Section: Rna Preparation and Reversementioning

confidence: 99%

ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein

Liu

Kong

et al. 2006

Journal of Biological Chemistry

Self Cite

101

167

View full text Add to dashboard Cite

Loss of articular cartilage because of extracellular matrix breakdown is the hallmark of arthritis. Degradative fragments of cartilage oligomeric matrix protein (COMP), a prominent noncollagenous matrix component in articular cartilage, have been observed in the cartilage, synovial fluid, and serum of arthritis patients. The molecular mechanism of COMP degradation and the enzyme(s) responsible for it, however, remain largely unknown. ADAMTS-12 (a disintegrin and metalloprotease with thrombospondin motifs) was shown to associate with COMP both in vitro and in vivo. ADAMTS-12 selectively binds to only the epidermal growth factorlike repeat domain of COMP of the four functional domains tested. The four C-terminal TSP-1-like repeats of ADAMTS-12 are shown to be necessary and sufficient for its interaction with COMP. Recombinant ADAMTS-12 is capable of digesting COMP in vitro. The COMP-degrading activity of ADAMTS-12 requires the presence of Zn 2؉ and appropriate pH (7.5-9.5), and the level of ADAMTS-12 in the cartilage and synovium of patients with both osteoarthritis and rheumatoid arthritis is significantly higher than in normal cartilage and synovium. Together, these findings indicate that ADAMTS-12 is a new COMP-interacting and -degrading enzyme and thus may play an important role in the COMP degradation in the initiation and progression of arthritis.More than 15% of the world population older than 18 years are affected by arthritic disorders, including osteoarthritis (OA) 3 and rheumatoid arthritis (RA) (1). Accumulating evidence suggests that proteases perform an important function in the breakdown of the extracellular matrix in OA and RA (2). Cartilage oligomeric matrix protein (COMP), a prominent noncollagenous component of cartilage, accounts for ϳ1% of the wet weight of articular tissue (3, 4). COMP is a 524-kDa pentameric, disulfide-bonded, multidomain glycoprotein composed of approximately equal subunits (ϳ110 kDa each) (5, 6). Several studies suggest that monitoring of COMP levels (in both joint fluid and serum) can be used to assess the presence and progression of arthritis (7-11). Synovial fluid COMP levels were found to be higher in individuals with knee pain or injury (12), anterior cruciate ligament or meniscal injury (9, 12), OA (8, 12), and RA (7, 13) than in healthy individuals.Fragments of COMP have been detected in the cartilage, synovial fluid, and serum of patients with post-traumatic and primary OA and RA (7,8,13). The molecular mechanism of COMP degradation and the enzyme (s) responsible for it, however, remain largely unknown. Theoretically, inhibition of degradative enzymes can slow down or block the initiation and progression of arthritic diseases. The isolation of cartilage degradative enzymes is therefore of great interest from both a pathophysiological and a therapeutic standpoint. The ADAMTS family (ADAMTS: (a disintegrin and metalloprotease with thrombospondin motifs) consists of secreted zinc metalloproteinases with a precisely ordered modular organization that includes at least o...

show abstract

Expression of bone morphogenetic proteins, receptors, and tissue inhibitors in human fetal, adult, and osteoarthritic articular cartilage

Cited by 50 publications

References 19 publications

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

ADAMTS‐7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein

Bone morphogenetic protein-7 expression is down-regulated in human clear cell renal carcinoma

ADAMTS-12 Associates with and Degrades Cartilage Oligomeric Matrix Protein

Contact Info

Product

Resources

About