[Expression of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues of rapidly destructive coxarthropathy (RDC), analyzed by immunohistochemical study].
OBJECTIVE
Rapidly destructive coxarthropathy (RDC) is characterized by rapid destruction of hip joints, but its pathogenetic mechanism is still obscure. Matrix metalloproteinases (MMPs) are possibly one of the candidates concerning with this mechanism. We attempted histochemical investigation to demonstrate MMPs and tissue inhibitor of metalloproteinases (TIMPs) in joint tissues obtained from RDC patients to clarify their roles in the destruction mechanism.


METHODS
Joint tissues including synovia and cartilage-bone tissues were obtained from RDC patients at total hip replacement (THR). After fixation with 4% paraformaldehyde, cartilage-bone tissues were partly decalcified. We performed histochemical study for paraffin sections of these tissues by using avidin-biotin method. Antibodies used in this study were monoclonal antibodies to MMP-1, MMP-2, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2 and polyclonal antibody to MMP-3.


RESULTS
Histological feature of RDC was severe destruction of cartilage and bone by invasion of non-specific granulation tissues composed of many small vessels, macrophages and fibroblastic cells. At the same time, RDC showed apparently fewer lymphocytic cells in these granulation tissues compare with rheumatoid arthritis. MMP-2 and MMP-9 were expressed most demonstrably in synovia and destructive regions of femoral heads, especially in osteoclasts, macrophages, and fibroblastic cells, while MMP-1, MMP-3, were slightly expressed only in the superficial layer of synovia in limited cases. MMP-8, usually contained in neutrophils, was not present in RDC. On the other hand TIMP-1 and TIMP-2 were presented throughout the synovia and destructive regions of femoral heads including fibroblastic cells, macrophages, osteoblasts and osteocytes.


CONCLUSIONS
Immunohistochemical study revealed obvious presence of MMP-2 and MMP-9 in synovia and destructive regions of femoral heads in RDC. Those evidence suggest that MMP-2 and MMP-9 share very important role in the destructive mechanism of RDC, possibly under imbalance between TIMPs.
Matsumoto
F
F
Department of Orthopaedic Surgery, Naruko National Hospital, Miyagi.
Uzuki
M
M
Kaneko
C
C
Rikimaru
A
A
Kokubun
S
S
Sawai
T
T
D000368:Aged; D000369:Aged, 80 and over; D017364:Collagenases / Q000378:metabolism*; D005260:Female; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007596:Joints / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020783:Matrix Metalloproteinase 7; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D008666:Metalloendopeptidases / Q000378:metabolism*; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000201:enzymology* / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*
D019714:Tissue Inhibitor of Metalloproteinases; D017364:Collagenases; D018093:Gelatinases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7; D020778:Matrix Metalloproteinase 2; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1