Expression profile of matrix metalloproteinase-2 and -9 and their endogenous tissue inhibitors in osteonecrotic femoral heads.
The pathogenetic mechanisms of osteonecrosis of the femoral head are unresolved to date. This study analyzed the matrix metalloprotease (MMP) and tissue inhibitor of matrix metalloprotease (TIMP) expression and activity which might add to the impaired bone matrix repair capacity affecting the balance between bone resorption and de novo bone formation in osteonecrosis of the femoral head (ONFH). Cancellous bone biopsies were taken at the femoral head and neck of patients with advanced ONFH and patients with primary osteoarthritis (OA) who were undergoing total hip arthroplasty. We assessed the gene expression levels of MMP-2 and -9, TIMP-1 and -2, Il-1beta, Il-6 and TNF-alpha in both biopsies. These data were corroborated by MMP activity screening, collagen profiling and ELISAs for determination of MMP, TIMP, Il-1beta, Il-6 and TNF-alpha concentrations. Gene expression rates of MMP-2 and TIMP-1 were higher in ONFH biopsies whereas TIMP-2 and MMP-9 gene expression was not significantly altered. MMP protein profile shifted towards increased biosynthesis of both, active and pro-MMP-2 in ONFH bone lysates and decreased pro-MMP-9 production. Expression profiles of pro-inflammatory cytokines and collagens in OA and ONFH bone lysates were highly similar. Increased biosynthesis and activation of MMP-2 in ONFH samples may add to shifting the bone matrix turnover balance towards resorption of bone macromolecules thereby counter-acting new bone matrix production. OA- and ONFH-affected bone exhibits a similar pro-inflammatory cytokine and collagen expression profile suggesting a relationship on the molecular level of inflammation and collagenous matrix composition between both diseases.
Grässel
Susanne
S
Department of Orthopaedic Surgery, University of Regensburg, D-93053 Regensburg, Germany. susanne.graessel@klinik.uni-regensburg.de
Beckmann
Johannes
J
Rath
Björn
B
Vogel
Mandy
M
Grifka
Joachim
J
Tingart
Markus
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005271:Femur Head Necrosis / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics / Q000378:metabolism; D010020:Osteonecrosis / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics* / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D053583:Interleukin-1beta; D015850:Interleukin-6; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9