Calcified Tissue International

, Volume 76, Issue 5, pp 326–335 | Cite as

Localization of Matrix Metalloproteinases, (MMPs) Their Tissue Inhibitors, and Vascular Endothelial Growth Factor (VEGF) in Growth Plates of Children and Adolescents Indicates a Role for MMPs in Human Postnatal Growth and Skeletal Maturation

  • G. Haeusler
  • I. Walter
  • M. Helmreich
  • M. Egerbacher
Article

Abstract

Numerous studies have focused on the expression, regulation, and biological significance of matrix metalloproteinases (MMPs) in the growth plate. Findings in mouse knockout models and in vitro data from various species indicate that MMPs not only degrade extracellular matrix components but may regulate the activity of local growth factors. In this study we investigated the presence, distribution, and activity of various MMPs and inhibitors, tissue transglutaminase (tTG or TG2) and vascular endothelial growth factor (VEGF) in the human child and adolescent growth plates by means of immunohistochemistry and gelatin zymography. Tissue was derived during orthopedic surgery (epiphysiodesis) in two prepubertal and four pubertal patients.

MMP-2 and MMP-14 were present in reserve cell chondrocytes. MMP-14 was the most prominent MMP within all zones of the growth plate including proliferating chondrocytes. MMP-1 and MMP-13 (collagenases 1 and 3), MMP-9 (gelatinases B), MMP-10, and MMP-11 (stromelysins) and VEGF were positive in hypertrophic chondrocytes and osteoblasts. MMP-2 showed the same expression pattern but was negative in osteoblasts. Osteoclasts stained positive for MMP-9, MMP-2, and TG2. Tissue inhibitor of MMP (TIMP)-1 was present in all zones of the growth plate, osteoblasts, and osteoclasts; TIMP-2 was found in hypertrophic chondrocytes and osteoblasts. In summary, the presence of MMPs, TIMPs, TG2, and VEGF in our study indicated that the MMPs are relevant in growth plate physiology during the postnatal period in humans. The specific location of MMP expression within the growth plate may be the basis for further studies on the role of MMPs in the local regulation of chondrocyte differentiation, proliferation, and ossification at the chondroosseus junction.

Keywords

Human growth plate Metalloproteinases VEGF Immunohistochemistry Gelatin zymography 

Notes

Acknowledgment

The authors are indepted to Prof. F. Grill and Dr. H. Manner from the Orthopedic Hospital Speising, Vienna, for their collaboration, and Waltraud Tschulenk for technical assistance.

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Copyright information

© Springer Science+Business Media, Inc. 2005

Authors and Affiliations

  • G. Haeusler
    • 1
  • I. Walter
    • 2
  • M. Helmreich
    • 2
  • M. Egerbacher
    • 2
  1. 1.Pediatric DepartmentMedical University of ViennaAustria
  2. 2.Pathobiology Department, Institute of Histology and EmbryologyUniversity of Veterinary MedicineAustria

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