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Lysyl Oxidase (Lox) Gene Deficiency Affects Osteoblastic Phenotype

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Abstract

Lysyl oxidase (LOX) catalyzes cross-linking of elastin and collagen, which is essential for the structural integrity and function of bone tissue. The present study examined the role of Lox gene deficiency for the osteoblast phenotype in primary calvarial osteoblasts from E18.5 Lox knockout (Lox −/−) and wild type (wt) (C57BL/6) mice. Next to Lox gene depletion, mRNA expression of Lox isoforms, LOXL1–4, was significantly downregulated in Lox −/− bone tissue. A significant decrease of DNA synthesis of Lox −/− osteoblasts compared to wt was found. Early stages of osteoblastic apoptosis studied by annexin-V binding as well as later stages of DNA fragmentation were not affected. However, mineral nodule formation and osteoblastic differentiation were markedly decreased, as revealed by significant downregulation of osteoblastic markers, type I collagen, bone sialoprotein, and Runx2/Cbfa1.

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Acknowledgements

We thank B. Danielowski and V. Kanitz for the technical support in the laboratory. This study was supported by grant DE140066 (to P. T.), grants 202469 from the Health Science Council and the S. Juselius Foundation (to J. M.), research stipend German Research Foundation GK-325-00 (to P.M. and N.H.), as well as short-term research fellowships from European Molecular Biology Organization and European Cooperation in Science and Technology, a habilitation stipend from the Charité – Universitätsmedizin Berlin, and research grant DFG PI 420/3 (to N.P.).

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Authors and Affiliations

  1. Department of Operative Dentistry and Periodontology, CharitéCentrum 3, University School of Dental Medicine, Charité – Universitätsmedizin Berlin, Aβmannshauserstraβe 4-6, 14197, Berlin, Germany

    N. Pischon, P. Weisshaupt, N. Heng, A. M. Kielbassa, B. M. Kleber & J.-P. Bernimoulin

  2. Oulu Center for Cell-Matrix Research, Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, Oulu, Finland

    J. M. Mäki & J. Myllyharju

  3. Department of Oral Biology and Periodontology, Goldman School of Dental Medicine, Boston University, Boston, MA, USA

    A. H. Palamakumbura & P. C. Trackman

  4. Department of Infectious Diseases and Pulmonology, Charité – Universitätsmedizin, Berlin, Germany

    P. N’Guessan

  5. Department of Experimental Dental Medicine, Charité – Universitätsmedizin, Berlin, Germany

    A. Ding, R. Radlanski & H. Renz

  6. Department of Oral Cell Biology, ACTA, Vrije Universiteit, Amsterdam, The Netherlands

    T. A. L. J. J. Bronckers

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  1. N. Pischon
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Correspondence to N. Pischon.

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Pischon, N., Mäki, J.M., Weisshaupt, P. et al. Lysyl Oxidase (Lox) Gene Deficiency Affects Osteoblastic Phenotype. Calcif Tissue Int 85, 119–126 (2009). https://doi.org/10.1007/s00223-009-9252-8

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