Experimental studies on the effects of recombinant human matrix metalloproteinases on herniated disc tissues--how to facilitate the natural resorption process of herniated discs.
OBJECTIVE
Recently, MMP-7 and MMP-3 have been found to play a crucial role in the natural resorption process of herniated discs. We therefore examined the role of these recombinant human matrix metalloproteinases (rh MMPs) in the treatment of herniated discs.


METHODS
(a) Surgical samples of herniated disc were cultured in the presence or absence of rh MMPs, and wet weight was measured 24h later. (b) The rh MMPs were administered into normal rabbit intervertebral discs, and after 1 week spine samples were stained with Safranin O. (c) The rh MMPs were administered into canine herniated discs in vivo. Myelography and MRI were performed prior to and 1 week after administration. Spine samples were examined histologically. Whole disc tissue was collected, total protein was extracted, and Western blot analysis was performed.


RESULTS
(a) Proteoglycan degradation was found in MMP-7, MMP-3, and chymopapain-treated samples. MMP-7 and chymopapain-treated samples displayed a significant loss in wet weight (p<0.01). (b) Normal disc tissues after administration of rh MMP-7, MMP-3, and chymopapain showed an extensive loss of Safranin O staining. (c) The rh MMP-7-treated discs had a marked decrease in protruded herniation by MRI. Herniated discs after administration of MMP-7 and chymopapain showed a significant decrease in protruded mass 7 days after administration compared with saline-treated discs when evaluated by myelography (p<0.01). The rh MMP-7-treated discs displayed a clear loss of Safranin O staining in the nucleus pulposus. Proteoglycan expression was barely detectable in disc tissues after MMP-7 administration, whereas obvious expression was obtained in saline-treated or untreated disc tissues.


CONCLUSIONS
Exposure to rh MMP-7 resulted in promising proteoglycan loss in human surgical samples, normal rabbit intervertebral discs, and natural canine herniated discs. Administration of rh MMP-7 may facilitate the resorption process of herniated discs.
Haro
Hirotaka
H
Department of Orthopaedic Surgery, Suwa Central Hospital, 4300 Tamagawa, Chino, Nagano 391-8503, Japan. haro.orth@tmd.ac.jp
Komori
Hiromichi
H
Kato
Tsuyoshi
T
Hara
Yasushi
Y
Tagawa
Masahiro
M
Shinomiya
Kenichi
K
Spengler
Dan M
DM
D000328:Adult; D000818:Animals; D002917:Chymopapain / Q000627:therapeutic use; D004285:Dogs; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism; D007405:Intervertebral Disc Displacement / Q000188:drug therapy*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000627:therapeutic use; D020783:Matrix Metalloproteinase 7 / Q000494:pharmacology / Q000627:therapeutic use*; D008875:Middle Aged; D009924:Organ Culture Techniques; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D011994:Recombinant Proteins / Q000627:therapeutic use
D011509:Proteoglycans; D011994:Recombinant Proteins; D002917:Chymopapain; D019278:Matrix Metalloproteinase 3; D020783:Matrix Metalloproteinase 7