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MMP-9 and CD68+ cells are required for tissue remodeling in response to natural hydroxyapatite

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Abstract

Large bone defects represent major clinical problems in the practice of reconstructive orthopedic and craniofacial surgery. The aim of this study was to examine, through immunohistochemistry approach, the involvement of MMP-9 and CD68+ cells during tissue remodeling in response to natural hydroxyapatite (HA) implanted in rat subcutaneous tissue. Before experimentation, forty animals were randomly distributed into two experimental groups: Group-I (Gen-Ox™ micro-granules) and Group-II (Gen-Ox™ macro-granules). Afterwards, the biopsies were collected after 10, 20, 30, and 60 days post-implantation. Our results showed that at 10 days, a low-renewal foreign body type granuloma formation was observed in most of the cases. Macrophage- and fibroblast-like cells were the predominant type of cells positively stained for MMP-9 in both groups. Once macrophage-like cells seemed to be the major source of MMP9, antibody against pan-CD68 epitope was used to correlate these findings. In agreement, MMP-9 and CD68+ cells were distributed at the periphery and the central region of the granuloma in all experimental periods, however no staining was observed in cell contacting to material. Besides macrophages, the lysosomal glycoprotein epitope recognized by CD68 antibodies can be expressed by mast cell granules and sometimes by fibroblasts. Taken together, our results suggest that xenogenic HA promotes extracellular matrix remodeling through induction of MMP-9 activity and presence of CD68+ cells.

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Acknowledgments

We would like to thank Tania M. Cestari and Danielle S. Ceolin for exceptional technician support. This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (W.F.Z., 08/53003-9).

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Authors and Affiliations

  1. Department of Biochemistry, IB, University of Campinas, Campinas, SP, Brazil

    Willian F. Zambuzzi

  2. Department of Oral Pathology, São Paulo Dental School, São Paulo, SP, Brazil

    Katiúcia B. S. Paiva

  3. Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA

    Renato Menezes

  4. Department of Biological Sciences, Bauru Dental School, University of Sao Paulo, Bauru, SP, Brazil

    Rodrigo C. Oliveira & Rumio Taga

  5. Department of Cell and Molecular Biology, IB, Fluminense Federal University, Niterói, RJ, Brazil

    José M. Granjeiro

  6. Cell and Molecular Therapy Center, University of Sao Paulo, São Paulo, SP, Brazil

    José M. Granjeiro

  7. Department of Cell and Molecular Biology, UFF, Av. Outeiro de São João Baptista, s/n, Campus do Valonguinho, Niterói, Rio de Janeiro, 24 020-150, Brazil

    José M. Granjeiro

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  1. Willian F. Zambuzzi
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  2. Katiúcia B. S. Paiva
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  6. José M. Granjeiro
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Correspondence to José M. Granjeiro.

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Zambuzzi, W.F., Paiva, K.B.S., Menezes, R. et al. MMP-9 and CD68+ cells are required for tissue remodeling in response to natural hydroxyapatite. J Mol Hist 40, 301–309 (2009). https://doi.org/10.1007/s10735-009-9241-2

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  • DOI: https://doi.org/10.1007/s10735-009-9241-2

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