The role of bone sialoprotein in the tendon-bone insertion

Ryan Marinovich; Yohannes Soenjaya; Gregory Q Wallace; Andre Zuskov; Andrew Dunkman; Brian L Foster; Min Ao; Kevin Bartman; Vida Lam; Amin Rizkalla; Frank Beier; Martha J Somerman; David W Holdsworth; Louis J Soslowsky; François Lagugné-Labarthet; Harvey A Goldberg

doi:10.1016/j.matbio.2016.01.016

The role of bone sialoprotein in the tendon-bone insertion

Matrix Biol. 2016 May-Jul:52-54:325-338. doi: 10.1016/j.matbio.2016.01.016. Epub 2016 Jan 28.

Authors

Ryan Marinovich¹, Yohannes Soenjaya², Gregory Q Wallace³, Andre Zuskov⁴, Andrew Dunkman⁴, Brian L Foster⁵, Min Ao⁶, Kevin Bartman¹, Vida Lam⁷, Amin Rizkalla⁸, Frank Beier⁹, Martha J Somerman⁶, David W Holdsworth¹⁰, Louis J Soslowsky⁴, François Lagugné-Labarthet³, Harvey A Goldberg¹¹

Affiliations

¹ Department of Biochemistry, University of Western Ontario, London, ON, Canada.
² Biomedical Engineering Program, University of Western Ontario, London, ON, Canada.
³ Department of Chemistry, University of Western Ontario, London, ON, Canada.
⁴ McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, PA, USA.
⁵ Division of Biosciences, College of Dentistry, The Ohio State University, Columbus, OH, USA.
⁶ National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), National Institutes of Health (NIH), Bethesda, MD, USA.
⁷ School of Dentistry, University of Western Ontario, London, ON, Canada.
⁸ Biomedical Engineering Program, University of Western Ontario, London, ON, Canada; School of Dentistry, University of Western Ontario, London, ON, Canada.
⁹ Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada.
¹⁰ Departments of Surgery and Medical Biophysics, University of Western Ontario, London, ON, Canada.
¹¹ Department of Biochemistry, University of Western Ontario, London, ON, Canada; School of Dentistry, University of Western Ontario, London, ON, Canada. Electronic address: hagoldbe@uwo.ca.

Abstract

Tendons/ligaments insert into bone via a transitional structure, the enthesis, which is susceptible to injury and difficult to repair. Fibrocartilaginous entheses contain fibrocartilage in their transitional zone, part of which is mineralized. Mineral-associated proteins within this zone have not been adequately characterized. Members of the Small Integrin Binding Ligand N-linked Glycoprotein (SIBLING) family are acidic phosphoproteins expressed in mineralized tissues. Here we show that two SIBLING proteins, bone sialoprotein (BSP) and osteopontin (OPN), are present in the mouse enthesis. Histological analyses indicate that the calcified zone of the quadriceps tendon enthesis is longer in Bsp(-/-) mice, however no difference is apparent in the supraspinatus tendon enthesis. In an analysis of mineral content within the calcified zone, micro-CT and Raman spectroscopy reveal that the mineral content in the calcified fibrocartilage of the quadriceps tendon enthesis are similar between wild type and Bsp(-/-) mice. Mechanical testing of the patellar tendon shows that while the tendons fail under similar loads, the Bsp(-/-) patellar tendon is 7.5% larger in cross sectional area than wild type tendons, resulting in a 16.5% reduction in failure stress. However, Picrosirius Red staining shows no difference in collagen organization. Data collected here indicate that BSP is present in the calcified fibrocartilage of murine entheses and suggest that BSP plays a regulatory role in this structure, influencing the growth of the calcified fibrocartilage in addition to the weakening of the tendon mechanical properties. Based on the phenotype of the Bsp(-/-) mouse enthesis, and the known in vitro functional properties of the protein, BSP may be a useful therapeutic molecule in the reattachment of tendons and ligaments to bone.

Keywords: Bone sialoprotein; Calcified fibrocartilage; Enthesis; Osteopontin; Quadriceps tendon; Supraspinatus tendon.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Animals
Bone and Bones / metabolism
Bone and Bones / ultrastructure*
Calcification, Physiologic
Integrin-Binding Sialoprotein / metabolism*
Mice
Osteopontin / metabolism*
Spectrum Analysis, Raman
Tendons / metabolism
Tendons / ultrastructure*
X-Ray Microtomography

Substances

Ibsp protein, mouse
Integrin-Binding Sialoprotein
Spp1 protein, mouse
Osteopontin

Abstract

Publication types

MeSH terms

Substances

Grants and funding