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Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development

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Abstract

Heparan sulfate proteoglycans (HSPGs) are abundant in the pericellular matrix of both developing and mature cartilage. Increasing evidence suggests the action of numerous chondroregulatory molecules depends on HSPGs. In addition to specific functions attributed to their core protein, the complexity of heparan sulfate (HS) synthesis provides extraordinary structural and functional heterogeneity. Understanding the interactions of chondroregulatory molecules with HSPGs and their subsequent outcomes has been limited by the absence of a detailed analysis of HS species in cartilage. In this study, we characterize the distribution and variety of HS species in developing cartilage of normal mice. Cryo-sections of femur and tibia from normal mouse embryos were evaluated using immunostaining techniques. A panel of unique phage display antibodies specific to particular HS species were employed and visualized with secondary antibodies conjugated to Alexa-fluor dyes. Confocal microscopy demonstrates that HS species are dynamic structures within developing growth plate cartilage and the perichondrium. GlcNS6S-IdoUA2S-GlcNS6S species are down regulated and localization of GlcNS6S-IdoUA-GlcNS6S species within the hypertrophic zone of the growth plate is lost during normal development. Regional differences in HS structures are present within developing growth plates, implying that interactions with and responses to HS-binding proteins also may display regional specialization.

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Acknowledgments

We greatly appreciate discussion of these data with Dr. Jin-Ping Li, and Dr. Ulf Lindahl. The authors thank Mr. Michael Alicknavitch, Dr. Kirk Czymmek, and Ms. JoAnne Julian for helpful technical assistance and suggestions. We also thank Ms. Sharron (“Sarge”) Kingston and Mrs. Doreen Anderson for outstanding assistance in preparing this work for publication. These studies were supported by NIH: R01 DE13542 (to D.D.C. and M.C.F-C.) and NIH NRSA: F32 AG20078, and NIH-P20-PR16458 (to R.R.G.) and M.C.F-C.).

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  1. Ronald R. Gomes Jr

    Present address: Department of Orthopaedics and Rehabilitation, Penn State College of Medicine Hershey, Hershey, PA, 17033, USA

Authors and Affiliations

  1. Department of Biological Sciences, University of Delaware Newark, Newark, DE, 19716, USA

    Ronald R. Gomes Jr, Mary C. Farach-Carson & Daniel D. Carson

  2. Department of Biochemistry, University Medical Center, NCMLS, Nijmegen, The Netherlands

    Toin H. Van Kuppevelt

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  1. Ronald R. Gomes Jr
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Correspondence to Daniel D. Carson.

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Gomes, R.R., Van Kuppevelt, T.H., Farach-Carson, M.C. et al. Spatiotemporal distribution of heparan sulfate epitopes during murine cartilage growth plate development. Histochem Cell Biol 126, 713–722 (2006). https://doi.org/10.1007/s00418-006-0203-4

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