The role of bone sialoprotein in the tendon-bone insertion

Tendons and ligaments insert into bone through a transitional tissue termed the enthesis which is susceptible to injury and difficult to repair. Entheses contain a region of calcified fibrocartilage (CFC), however mineral-associated proteins in this tissue remain poorly characterized. Bone sialoprotein (BSP) is a phosphoprotein associated with mineralizing tissues. In these studies BSP was identified in the CFC of entheses by immunohistochemistry. Analysis of the entheses of Bsp-/- mice indicate abnormalities in the CFC. Compared to controls, the CFC of the quadriceps tendon enthesis is 28% and 41 % longer in 15 week and 14 month old Bsp-/- mice, respectively. MicroCT and Raman spectroscopic analysis of the CFC in Bsp-/- mice demonstrate that mineral content is similar between genotypes. Mechanical studies show that the Bsp-/- patellar tendon is larger in cross-sectional area yet mechanically weaker. These data suggest BSP is involved in the regulation and growth of the CFC

The "linked evidence approach" to assess medical tests: a critical analysis

Objectives: A linked evidence approach (LEA) is the synthesis of systematically acquired evidence on the accuracy of a medical test, its impact on clinical decision making and the effectiveness of consequent treatment options. We aimed to assess the practical utility of this methodology and to develop a decision framework to guide its use. Methods: As Australia has lengthy experience with LEA, we reviewed health technology assessment (HTA) reports informing reimbursement decisions by the Medical Services Advisory Committee (August 2005 to March 2012). Eligibility was determined according to predetermined criteria and data were extracted on test characteristics, evaluation methodologies, and reported difficulties. Fifty percent of the evidence-base was independently analyzed by a second reviewer. Results: Evaluations of medical tests for diagnostic (62 percent), staging (27 percent), and screening (6 percent) purposes were available for eighty-nine different clinical indications. Ninety-six percent of the evaluations used either the full LEA methodology or an abridged version (where evidence is linked through to management changes but not patient outcomes). Sixty-one percent had the full evidence linkage. Twenty-five percent of test evaluations were considered problematic; all involving LEA (n = 22). Problems included: determining test accuracy with an imperfect reference standard (41 percent); assessing likely treatment effectiveness in test positive patients when the new test is more accurate than the comparator (18 percent); and determining probable health benefits in those symptomatic patients ruled out using the test (13 percent). A decision framework was formulated to address these problems. Conclusions: LEA is useful for evaluating medical tests but a stepped approach should be followed to determine what evidence is required for the synthesis.Tracy Merlin, Samuel Lehman, Philip Ryan, Janet E. Hille

The role of bone sialoprotein in the tendon-bone insertion

© 2016 International Society of Matrix Biology. 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