The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants

Larry W. Hunter, John C Lieske, Nho V. Tran, Virginia M Miller

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8364-8373
Number of pages10
JournalBiomaterials
Volume32
Issue number33
DOIs
StatePublished - Nov 2011

Fingerprint

Breast Implants
Silicones
Isomers
Capsules
Association reactions
Prosthetics
Proteins
alpha-2-HS-Glycoprotein
Vitamins
Tissue
Vitamin K
Calcification (biochemistry)
Prostheses and Implants
Minerals
Glycoproteins
Mineral resources
Fibers
Silicone Gels
Calcinosis
Collagen

Keywords

  • Biocompatibility
  • Calcification
  • Foreign-body response
  • Hydroxyapatite
  • Nanoparticle
  • Silicone

ASJC Scopus subject areas

  • Biomaterials
  • Bioengineering
  • Ceramics and Composites
  • Mechanics of Materials
  • Biophysics

Cite this

The association of matrix Gla protein isomers with calcification in capsules surrounding silicone breast implants. / Hunter, Larry W.; Lieske, John C; Tran, Nho V.; Miller, Virginia M.

In: Biomaterials, Vol. 32, No. 33, 11.2011, p. 8364-8373.

Research output: Contribution to journalArticle

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