Forsprecher et al. [172] |
In vitro |
MC3T3-E1/C4 osteoblastic cell |
To examine effects of tissue transglutaminase-mediated crosslinking and oligomerization of OPN and BSP on osteoblast cell adhesion |
Surfaces coated with oligomerized OPN and BSP promote MC3T3-E1/C4 osteoblastic cell adhesion significantly better than surfaces coated with the monomeric form of the proteins |
Li et al. [207] |
In vitro |
Human prostate cancer DU145 cells |
To investigate the effects of cAMP and FGF2 on BSP |
FSK and FGF2 stimulate BSP transcription in DU145 human prostate cancer cells by targeting the CRE1 and CRE2 elements in the human BSP gene promoter |
Sasaki et al. [209] |
In vitro |
Rat osteoblast-like ROS17/2.8 cells |
To investigate the effects of CO2 laser irradiation on BSP gene transcription |
CO2 laser irradiation increases BSP transcription via FRE in the rat BSP gene promoter |
Wang et al. [63, 189, 208] |
In vitro |
Rat BSP gene promoter |
To analyze the effects of IL-11 on the expression of the BSP gene in osteoblast-like cells |
IL-11 stimulates BSP transcription by targeting CRE, FRE, and HOX sites in the proximal promoter of the rat BSP gene. Moreover, phospho-CREB1, c-Fos, c-Jun, JunD, Fra2, Dlx5, Msx2, Runx2, and Smadl transcription factors appear to be key regulators of IL-11 effects on BSP transcription |
Wang et al. [63, 189, 208] |
In vitro |
Human osteoblast-like SaOS-2 cells |
To detail the mechanism involved in the mineralization induced by Ca(OH)(2) |
Ca(OH)(2) stimulates BSP transcription by targeting the CRE1, CRE2, and FRE elements in the human BSP gene promoter |
Xia et al. [192] |
In vitro |
Human BMSCs |
To investigate the effects of recombinant human BSP on the proliferation and osteodifferentiation of human BMSCs |
BSP is capable of inhibiting hBMSCs proliferation and enhancing their osteogenic differentiation and mineralization in the presence of osteogenic medium |
Boudiffa et al. [199] |
In vivo |
Mice |
To investigate the effect of BSP deficiency to osteoclastogenesis and mineral resorption |
Lack of BSP affects both osteoclast formation and activity |
Chan et al. [214] |
In vitro |
Murine preosteoblastic cell line (MC3T3-E1) |
To evaluate modification of PCL/pHEMA surfaces with BSP |
Modification of surfaces with BSP significantly enhanced osteoblastic cell attachment and spreading, without compromising proliferation |
Li et al. [206] |
In vitro |
Rat osteoblast-like ROS17/2.8 cells |
To investigate the effects of P. gingivalis lipopolysaccharide on BSP transcription |
0.1 microg/ml suppressed, and 0.01 microg/ml P. gingivalis lipopolysaccharide increased BSP gene transcription mediated through CRE and FRE elements in the rat BSP gene promoter |
Monfoulet et al. [194] |
In vivo |
Mouse femur |
To compare the roles of BSP and OPN in the repair process |
BSP, but not OPN, plays a role in primary bone formation and mineralization of newly formed bone during the process of cortical bone healing |
Schaeren et al. [215] |
In vivo, in vitro |
BMSC and nude mice |
To test whether synthetic polymer-based porous scaffolds could support ectopic bone formation by human BMSC if coated with BSP |
BSP coating of a variety of substrates is not directly associated with an enhancement of osteoprogenitor cell differentiation in vitro or in vivo, and that presentation of BSP on polymeric materials is not sufficient to prime BMSC functional osteoblastic differentiation in vivo |
Wang et al. [203] |
In vitro |
Osteoblast-like ROS 17/2.8 cells |
To investigate the effects of inorganic polyphosphate on BSP |
Sodium phosphate glass type 25 stimulates BSP transcription by targeting FRE and HOX elements in the proximal promoter of the rat BSP gene |
Yang et al. [190, 204, 205] |
In vitro |
Rat osteoblast-like ROS17/2.8 cells |
To investigate the regulation of BSP transcription by butyric acid |
Butyric acid increases the transcription of the BSP gene mediated through FRE in the rat BSP gene promoter, and induces osteoblast activity in the early stage of bone formation |
Yang et al. [190, 204, 205] |
In vitro |
Rat osteoblast-like UMR106 cells |
To investigate the regulation of BSP transcription by kaempferol |
Kaempferol increased BSP gene transcription mediated through inverted CCAAT, CRE, and FRE elements in the rat BSP gene promoter, and could induce osteoblast activities in the early stage of bone formation |
Gordon et al. [195] |
In vitro |
Primary rat bone osteoblastic cells |
To determine the molecular mechanisms responsible for the BSP-mediated increase in osteoblastic differentiation |
Increased expression of BSP in osteoblast cells can increase expression of the osteoblast-related genes Runx2 and Osx as well as alkaline phosphatase and osteocalcin and increase matrix mineralization |
Malaval et al. [198] |
In vivo |
Mice femur |
To report that absence BSP impair cortical defect repair |
The absence of BSP delays bone repair at least in part by impairing both new bone formation and osteoclast activity |
Mezawa et al. [200] |
In vitro |
Osteoblast-like SaOS-2 and ROS17/2.8 cells |
To determine the molecular mechanisms PDGF regulation of human BSP gene transcription |
PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3), and SSRE1 elements in the human BSP gene promoter |
Bernards et al. [170, 171] |
In vitro |
MC3T3-E1 cell |
To compare the cell binding ability of adsorbed BSP and OPN specifically bound to hydroxyapatite |
There is a preference for cell binding to HAP with adsorbed BSP as compared to OPN, but not to a statistically significant level |
Bernards et al. [170, 171] |
In vitro |
MC3T3-E1 cell |
To examine and compare the orientation of BSP under similar circumstances with OPN |
OPN is more important than BSP for osteoblast adhesion to the collagen matrix |
Graf et al. [216] |
In vitro |
Osteoblast |
To compare BSP as a surface-coating material against the major organic and inorganic components of bone, collagen type I, and hydroxyapatite (TICER) |
BSP precoating of the rough TICER implant surface enhanced the osteoinductive effect much more than did collagen precoating |
Malaval et al. [197] |
In vivo |
BSP(-/-) mice |
To investigate the role of BSP in bone formation and osteoclastogenesis |
BSP deficiency impairs bone growth and mineralization, concomitant with dramatically reduced bone formation |
Takai et al. [202] |
In vitro |
Osteoblastic cell line ROS17/2.8 |
To report that AP1 binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2 |
FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter |
Valverde et al. [196] |
In vivo |
Homozygous transgenic mouse |
To determine the effects of BSP overexpression in bone metabolism |
Overexpression of BSP decreased osteoblast population and increased osteoclastic activity and leads to an uncoupling of bone formation and resorption, which in turn results in osteopenia and mild dwarfism in mice |
Gordon et al. [193] |
In vitro |
MC3T3E1 cell |
To demonstrate that BSP can stimulate osteoblast differentiation through RGD-mediated cell interactions to promote mineralization |
BSP may serve as a matrix-associated signal directly promoting osteoblast differentiation resulting in the increased production of a mineralized matrix |
Lamour et al. [210] |
In vitro |
Osteoblast-like SaOS-2 cells |
To investigate the role of Runx2 in the regulation of BSP expression |
Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation |
Karadag and Fisher [213] |
In vitro |
BMSCs and pre-osteoblasts |
To investigate the effect of BSP to osteogenic cell migration through basement membrane and collagen matrices |
Pre-osteoblasts and their BMSC precursors may use MMP-2/BSP/integrin complexes to disrupt matrix barriers during migration to their final destinations in vivo |
Kato et al. [212] |
In vitro |
Osteoblast-like ROS 17/2.8 cells |
To determine the molecular mechanisms involved in the suppression of bone formation |
LPS suppresses BSP gene transcription through protein kinase A and tyrosine kinase-dependent pathways and that the LPS effects are mediated through CRE and FRE elements in the proximal BSP gene promoter |
Nakajima et al. [211] |
In vitro |
Osteoblast-like ROS17/2.8 cells and rat stromal bone marrow cells (SBMC-D8) |
To investigate the effect of chlorpromazine on BSP gene transcription |
Chlorpromazine suppresses BSP gene transcription through tyrosine and MAP kinases-dependent pathways and that the chlorpromazine effects are mediated by CRE and FRE elements in the proximal promoter of the BSP gene |
Nakayama et al. [201] |
In vitro |
Osteoblast-like SaOS-2 and rat stromal bone marrow (RBMC-D8) cells |
To determine the molecular mechanism of IGF-I regulation of osteogenesis |
IGF-I stimulates BSP transcription by targeting the FRE and HOX elements in the proximal promoter of BSP gene |
Wang et al. [188] |
In vivo |
Rats |
To investigate the potential role of BSP in more complex in vivo environments |
BSP stimulates calcification and osteogenesis in a site-specific manner, and that local environment and the specificities of responding cells may play critical roles in the function of BSP in vivo |