Biomedical subjects

Minna Laitinen

Publications and source records attributed to Minna Laitinen.

4 recordsLinked to original sources

PubMed2006

Lipid oxidation may reduce the quality of a fresh-frozen bone allograft. Is the approved storage temperature too high?

BACKGROUND: International standards indicate that bone allografts for human use should be stored in a -40 degrees C or colder environment and the storage time should be up to 5 years. Bone allografts contain lipids which oxidate and become toxic with time. MATERIAL AND METHODS: We determined lipid oxidation in femoral head bone allografts by headspace gas chromatography at different storage temperatures and storage times. RESULTS: We found that lipid oxidation in fresh-frozen bone allograft was influenced by storage temperature and storage time. Lipid oxidation was significantly more rapid at -30 degrees C than at -70 degrees C. Even at -70 degrees C, however, some oxidation occurred but it was quite minimal after 3 years. INTERPRETATION: Because of the negative effects of lipid oxidation, we recommend a storage temperature of -70 degrees C or lower for bone allografts.

Bone Transplantation↗

PubMed2006

[Not Available].

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Journal Article↗

PubMed2003

Inhibition of matrix metalloproteinase-14 in osteosarcoma cells by clodronate.

BACKGROUND: Bisphosphonates reduce the bone metastasis formation and angiogenesis but the exact molecular mechanisms involved are unclear. Progelatinase A (proMMP-2; 78 KDa) is activated up during the tumor spread and metastasis by a cell surface-associated matrix metalloproteinase (membrane-type matrix metalloproteinase [MT1-MMP] or MMP-14). MATERIAL AND METHODS: We evaluated the effects of a bisphosphonate (clodronate) on MT1-MMP mRNA expression and protein production, catalytic activity and proteolytic activation of proMMP-2 by cultured human MG-63 osteosarcoma cells. RESULTS: Clodronate, at therapeutically attainable noncytotoxic concentrations, dose-dependently inhibited phorbol myristic acetate (PMA)-induced proteolytic activation of proMMP-2 by human MG-63 osteosarcoma cells. Clodronate also downregulated the PMA-induced expression of MT1-MMP mRNA and protein production in human MG-63 osteosarcoma cells, as evidenced by Northern analysis and fluorescent immunohistochemistry. Furthermore, clodronate inhibited directly and dose-dependently MT1-MMP activity, and the MT1-MMP inhibition by clodronate was reduced in the presence of an increased (5 mM) Ca(2+) concentrations when compared to physiological (1 mM) Ca(2+) concentrations. CONCLUSION: We conclude that (1) the extracellular/cell-associated mechanism of bisphosphonate involves inhibition of MT1-MMP catalytic activity eventually by chelation, and that (2) intracellular mechanism involves downregulation of induced MT1-MMP mRNA and protein expression. The inhibition and downregulation of MT1-MMP by clodronate can be related to their ability to reduce MG-63 osteosarcoma cell invasion and spread. These findings may, at least in part, explain at molecular level the antitumor and antibone resorption activities of clodronate observed in clinical studies.

Binding Sites↗

PubMed2002

Bisphosphonates inhibit stromelysin-1 (MMP-3), matrix metalloelastase (MMP-12), collagenase-3 (MMP-13) and enamelysin (MMP-20), but not urokinase-type plasminogen activator, and diminish invasion and migration of human malignant and endothelial cell lines.

Bisphosphonates (clodronate, alendronate, pamidronate and zoledronate) at therapeutically attainable non-cytotoxic concentrations inhibited MMP-3, -12, -13 and -20 as well as MMP-1, -2, -8 and -9, but not urokinase-type plasminogen activator (uPA), a serine proteinase and a pro-MMP activator. Dose-dependent inhibition was shown by three independent MMP assays. The inhibition was reduced in the presence of an increased concentration of Ca(2+) when compared to physiologic Ca(2+) concentration. Alendronate inhibited the in vitro invasion (Matrigel) of human HT1080 fibrosarcoma and C8161 melanoma cells, and the random migration of these malignant and endothelial cell lines capable of expressing MMPs and uPA. The concentration of alendronate required to inhibit 50% of the activity (IC(50)=40-70 microM) of MMPs corresponded to the IC(50) of down-regulation of in vitro invasion and migration. The ability of bisphosphonates to down-regulate the in vitro invasion and random migration was comparable or slightly better in relation to the selective gelatinase inhibitor CTTHWGFTLC peptide. Alendronate but not CTTHWGFTLC peptide promoted the adhesion of HT1080 fibrosarcoma and C8161 melanoma cell lines on fibronectin. Bisphosphonates are broad-spectrum MMP inhibitors and this inhibition involves cation chelation. Bisphosphonates further exert antimetastatic, anti-invasive and cell adhesion-promoting properties, which may prevent metastases not only into hard tissues but also to soft tissues.

Cell Adhesion↗