title: The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants.
abstract: Implanted silicone medical prostheses induce a dynamic sequence of histologic events in adjacent tissue resulting in the formation of a fibrotic peri-prosthetic capsule. In some cases, capsular calcification occurs, requiring surgical intervention. In this study we investigated capsules from silicone gel-filled breast prostheses to test the hypothesis that this calcification might be regulated by the small vitamin K-dependent protein, matrix Gla protein (MGP), a potent inhibitor of arterial calcification, or by Fetuin-A, a hepatocyte-derived glycoprotein also implicated as a regulator of pathologic calcification. Immunolocalization studies of explanted capsular tissue, using conformation-specific antibodies, identified the mineralization-protective γ-carboxylated MGP isomer (cMGP) within cells of uncalcified capsules, whereas the non-functional undercarboxylated isomer (uMGP) was typically absent. Both were upregulated in calcific capsules and co-localized with mineral plaque and adjacent fibers. Synovial-like metaplasia was present in one uncalcified capsule in which MGP species were differentially localized within the pseudosynovium. Fetuin-A was localized to cells within uncalcified capsules and to mineral deposits within calcific capsules. The osteoinductive cytokine bone morphogenic protein-2 localized to collagen fibers in uncalcified capsules. These findings demonstrate that MGP, in its vitamin K-activated conformer, may represent a pharmacological target to sustain the health of the peri-prosthetic tissue which encapsulates silicone breast implants as well as other implanted silicone medical devices.
authors.affiliation: Department of Surgery, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Larry W
authors.initials: LW
authors.lastname: Hunter
authors.forename: John C
authors.initials: JC
authors.lastname: Lieske
authors.forename: Nho V
authors.initials: NV
authors.lastname: Tran
authors.forename: Virginia M
authors.initials: VM
authors.lastname: Miller
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D018427:Breast Implants; D002114:Calcinosis; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D020034:Silicone Gels; D060749:alpha-2-HS-Glycoprotein / Q000378:metabolism; D000097568:Matrix Gla Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D020034:Silicone Gels; D060749:alpha-2-HS-Glycoprotein; D000097568:Matrix Gla Protein