title: Connective tissue growth factor is an indicator of bone involvement in multiple myeloma, but matrix metalloproteinase-9 is not.
abstract: Bone disease (BD) in multiple myeloma (MM) is because of the activation of osteoclasts and impairment of osteoblast differentiation. Connective tissue growth factor (CTGF) is known to participate in the differentiation of mesenchymal stem cells to committed osteoprogenitor cells. We analysed the concentration of circulating CTGF in 35 MM patients and 22 malignant lymphoma (ML) patients and 14 normal individuals. CTGF is protease-sensitive and thus is found as both an N-terminal half fragment (N-half CTGF) and whole (W-CTGF). Serum levels of W-CTGF and N-half CTGF + W-CTGF were determined by separate sandwich enzyme-linked immunosorbent assays. The level of W-CTGF was significantly lower (P < 0.005) in MM patients compared with ML patients and normal individuals, while N-half + W-CTGF was similar in all groups. Furthermore, W-CTGF was significantly lower in MM patients with BD compared with those without BD (P < 0.005) and this was independent of previous treatment. Matrix metalloproteinase (MMP)-9 is produced by myeloma cells and is thought to be related to BD in MM. However, MMP-9 does not cleave CTGF and serum MMP-9 level was not related to BD in MM. Thus, CTGF is an indicator of BD in MM; its metabolism and function in MM should be clarified.
authors.affiliation: Department of Haematology and Oncology, RIRBM, Hiroshima University, Hiroshima, Japan.
authors.forename: Shoso
authors.initials: S
authors.lastname: Munemasa
authors.forename: Akira
authors.initials: A
authors.lastname: Sakai
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Okikawa
authors.forename: Yuta
authors.initials: Y
authors.lastname: Katayama
authors.forename: Hideki
authors.initials: H
authors.lastname: Asaoku
authors.forename: Tadahiko
authors.initials: T
authors.lastname: Kubo
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Miyakawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Serikawa
authors.forename: Tamito
authors.initials: T
authors.lastname: Sasaki
authors.forename: Akiro
authors.initials: A
authors.lastname: Kimura
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001853:Bone Marrow / Q000737:chemistry / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D055513:Connective Tissue Growth Factor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D017874:Immediate-Early Proteins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood* / Q000235:genetics / Q000494:pharmacology; D008223:Lymphoma / Q000097:blood; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood* / Q000473:pathology; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D055513:Connective Tissue Growth Factor; D053509:Matrix Metalloproteinase 13; D020780:Matrix Metalloproteinase 9