The role of bone sialoprotein in the tendon–bone insertion

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.

Actein alleviates 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐mediated cellular dysfunction in osteoblastic MC3T3‐E1 cells

“…At the same time, actein markedly increased the expression of ALP, type I collagen, BSP, OPG, and osterix genes in the presence of TCDD. BSP appears following ALP expression and promotes the nucleation of hydroxyapatite mineralization, and then increases nodule formation . OPG, produced by osteoblasts, regulates bone metabolism and inhibits bone resorption by regulating osteoclast function .…”

Evaluation of Serum Levels of Osteopontin and Bone Sialoprotein in Female Patients with Tendinopathy

“…Mori et al revealed that OPN plays a crucial role in regulating tendon remodeling induced by stress deprivation and that OPN may act as a transducer of mechanical stress to the tendon fibroblasts [12]. Recently, Marinovich et al showed that OPN presents in the mouse enthesis [9]. In this study, we examined serum OPN levels in tendinopathy patients and we showed that no significant differences were found in serum OPN levels between tendinopathy patients and controls.…”

“…Also, Bellahcene et al demonstrated that BSP mediates human endothelial cell attachment and migration through the interaction of its RGD domain with endothelial cell integrin receptors and might be an important factor for the angiogenesis process in bone formation and tumour growth and metastasis [19]. In a recent 2016 study, Marinovich et al reported that BSP presents in the mouse enthesis and BSP plays a regulatory role in this structure [9]. In this study, we analyzed serum BSP levels in tendinopathy patients and we showed that no significant differences were found in serum BSP levels between tendinopathy patients and controls.…”

“…bones and teeth, but studies have revealed that they are more widely distributed and are also expressed in nonmineralized normal tissues such as salivary gland and kidney [6][7][8]. A recent study in 2016 showed that OPN and BSP-4 were present in enthesis; the study suggested that BSP plays a regulatory role in enthesis and may be a useful therapeutic molecule in the reattachment of tendons and ligaments to bone [9]. Musculoskeletal tissue cells, including osteoblasts, chondrocytes, myoblasts, and skin and tendon fibroblasts, share the common stem cells, differentiated mesenchymal stem cells [10,11].…”

Localized BMP-4 release improves the enthesis of engineered bone-to-bone ligaments

“…43 While SPARC expression remained unchanged, the expression of osteopontin, an acidic glycoprotein that inhibits mineralization, 44 was significantly increased (up to 155.5-fold) with BMP-4 (Figure 5I). Osteopontin has also recently been shown to be localized in the mouse supraspinatus and quadriceps tendon enthesis 45 in addition to being present at mineralized tissue interfaces of bone and cartilage 46 and regions of ectopic calcification in tendons. 47 Consistent with our gene expression analysis, Xu et al 48 have shown that aggrecan and osteopontin are upregulated in response to BMP-4 in periodontal ligament cells.…”