The Bone Sialoprotein RGD Domain Modulates and Maintains Periodontal Development

Abstract

Bone sialoprotein (gene: Ibsp; protein: BSP) is a multifunctional extracellular matrix protein present in bone, cementum, and dentin. Accumulating evidence supports BSP as a key regulator of mineralized tissue formation via evolutionarily conserved functional domains, including a C-terminal integrin-binding Arg-Gly-Asp (RGD) domain implicated in extracellular matrix–cell signaling. Ablation of Ibsp in mice ( Ibsp−/−) results in impaired bone growth and mineralization and defective osteoclastogenesis, with effects in the craniofacial region including reduced acellular cementum formation, detachment of the periodontal ligament (PDL), alveolar bone hypomineralization, and severe periodontal breakdown. We hypothesized that BSP-RGD plays an important role in cementum and alveolar bone formation and mineralization, as well as periodontal function. This hypothesis was tested by replacing the RGD motif with a nonfunctional Lys-Ala-Glu (KAE) sequence in ( IbspKAE/KAE) mice and OCCM.30 murine ( IbspKAE) cementoblasts. The RGD domain was not critical for acellular or cellular cementum formation in IbspKAE/KAE mice. However, PDL volume and thickness were increased, and significantly more tartrate-resistant acid phosphatase–positive osteoclasts were found on alveolar bone surfaces of IbspKAE/KAE mice versus wild type mice. PDL organization was disrupted as indicated by picrosirius red stain, second harmonic generation imaging, dynamic mechanical analysis, and decreased asporin proteoglycan localization. In vitro studies implicated RGD functions in cell migration, adhesion, and mineralization, and this was confirmed by an ossicle implant model where cells lacking BSP-RGD showed substantial defects as compared with controls. In total, the BSP-RGD domain is implicated in periodontal development, though the scale and scope of changes indicated by in vitro studies indicate that other factors may partially compensate for and reduce the phenotypic severity of mice lacking BSP-RGD in vivo.

Titanium micro-nano texturized surface with strontium incorporation improves osseointegration. An in vivo and in vitro study.

“…Geng et al (2022) [48] also obtained similar results and observed that Sr-loaded surface promoted an increase in osteopontin expression in vitro at four and seven days. Ibsp, which encodes bone sialoprotein-binding integrin, a multifunctional extracellular matrix protein present in bone, cementum, and dentin [50], followed the same pattern and was overexpressed in the MN and MNSr+ groups, while MNSr group was similar to control.…”

Comparative bioactivity and immunomodulatory potential of the new Bioroot Flow and AH Plus Bioceramic sealer: An in vitro study on hPDLSCs

“…CAP acts as an indicator of periodontium repair and regeneration, since its overexpression is observed during the formation of cement, specifically during cell recruitment and differentiation [ 62 , 63 ]. Parallelly, BSP acts as a tissue-specific indicator of mineralization, specifically expressed during the initial stages of osseous tissue formation [ 64 – 66 ]. Altogether, these results reflect the positive influence of BrF on the differentiation of hPDLSCs into a cemento/osteogenic lineage and its potential enhancement of periodontal/osseous tissue repair or regeneration.…”

Matrix Metalloproteinases in the Periodontium—Vital in Tissue Turnover and Unfortunate in Periodontitis

“…Cementum attachment protein is another collagenous protein [ 162 ]. Cementum contains many non-collagenous proteins, such as osteopontin, bone sialoprotein, matrix gamma-carboxyglutamic acid protein, osteocalcin, alkaline phosphatase, fibronectin, cementum-derived growing factor (CGF), cementum protein-1, and cementum enamel-associated proteins [ 161 , 163 , 164 ]. Glycosaminoglycan-containing proteoglycans seen in the cementum matrix are syndecan-1, syndecan-2, decorin, biglycan, fibromodulin, lumican, and versican [ 129 , 161 , 165 , 166 ].…”