Hidehiro Ozawa — Page 3

PubMed2002

Involvement of cyclo-oxygenase-2 in osteoclast formation and bone destruction in bone metastasis of mammary carcinoma cell lines.

We previously reported that mouse mammary carcinoma cell lines (MMT060562 and BALB/c-MC) induced osteoclast formation through production of prostaglandin E2 (PGE2) in cocultures with mouse bone marrow cells, but the mechanism(s) of PG production remained unclear. In the present in vitro and in vivo studies, we tested the involvement of cyclo-oxygenase-2 (COX-2), an inducible rate-limiting enzyme in PG biosynthesis, in the stimulation of osteoclast formation by mouse mammary carcinoma cell lines. Addition of a selective COX-2 inhibitor, JTE-522, to cocultures of mammary carcinoma cell lines and bone marrow cells lowered PGE2 concentration in the culture media and inhibited osteoclast formation in a dose-dependent manner. Northern blotting showed a very high level of COX-2 messenger RNA (mRNA) expression in MMT060562. The mRNA expression was low in BALB/c-MC, but it increased when BALB/c-MC and bone marrow cells were cocultured. The results of immunocytochemistry for COX-2 protein in respective cultures were compatible with the results of COX-2 mRNA. In vivo, BALB/c-MC injected into the heart of Balb/c mice metastasized to bone and formed osteolytic lesions in their hindlimbs. Histological examination revealed that tumor cells had metastasized to the bone marrow cavity and destroyed the bone trabeculae. Immunohistochemistry demonstrated that bone marrow stromal cells adjacent to tumor cells expressed COX-2 protein. These findings suggest that COX-2 plays an important role in the osteolysis of bone metastasis in vivo as well as in osteoclast formation in cocultures used as an in vitro model of metastatic bone disease.

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PubMedDate not supplied

Bone regeneration by recombinant human bone morphogenetic protein-2 around immediate implants: a pilot study in rats.

PURPOSE: Difficulties relating to bone regeneration that complicate immediate implant placement include buccal and/or lingual fenestrations, primary anchorage of the implants, and the need for protection from functional loading during the osseointegration period. The objective of this pilot study was to evaluate bone regeneration by recombinant human bone morphogenetic protein-2 (rhBMP-2) around immediate implants placed in maxillary sockets in rats. MATERIALS AND METHODS: A total of 16 cylindric 0.8 x 1.8-mm commercially pure, solid titanium Implants were placed immediately after gentle extraction of the maxillary first molar teeth of 8 male Wistar rats. The sockets were randomly divided into 3 groups: group 1 (n = 6) received rhBMP-2 with polylactic acid/polyglycolic acid copolymer-coated gelatin sponge carrier; group 2 (n = 5) received only the carrier; and group 3 (n = 5) received no grafting materials following placement The rats were euthanized at 90 days postsurgery for microscopic analysis. RESULTS: In group 1, the implant body remained submerged completely, including the coronal part, which was fully covered by a significant amount (30% of total height) of regenerated cortical bone, even though the implant could easily be pulled out by a tweezer at the time of placement. Close approximation between the implant surface and regenerated bone could also be detected, indicating good bone-to-implant contact. In contrast, only peri-implant bone regeneration occurred in group 2, and an approximate 0.3-mm coronal part of the implant remained exposed. When no grafting materials were used (group 3), almost one third of the total length of the implant was exfoliated out of the socket when no grafting materials were used. DISCUSSION AND CONCLUSIONS: Based on previous study and data from 16 sockets of the present study, it could be concluded that rhBMP-2 facilitated the regeneration of bone around immediate implants. In particular, the bone covering the coronal part could have been regenerated shortly after surgery, which helped to maintain the implant body inside the socket during the integration period in rats.

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