Role of osteopontin in bone remodeling and orthodontic tooth movement: a review

Amarjot Singh,Gurveen Gill,Mohamed Amhmed,Harsimrat Kaur,Harpal Jakhu

doi:10.1186/s40510-018-0216-2

Abstract

In this review, most of the known and postulated mechanisms of osteopontin (OPN) and its role in bone remodeling and orthodontic tooth movement are discussed based on available literature. OPN, a multifunctional protein, is considered crucial for bone remodeling, biomineralization, and periodontal remodeling during mechanical tension and stress (orthodontic tooth movement). It contributes to bone remodeling by promoting osteoclastogenesis and osteoclast activity through CD44- and αvβ3-mediated cell signaling. Further, it has a definitive role in bone remodeling by the formation of podosomes, osteoclast survival, and osteoclast motility. OPN has been shown to have a regulatory effect on hydroxyapatite crystal (HAP) growth and potently inhibits the mineralization of osteoblast cultures in a phosphate-dependent manner. Bone remodeling is vital for orthodontic tooth movement. Significant compressive and tensional forces on the periodontium induce the signaling pathways mediated by various osteogenic genes including OPN, bone sialoprotein, Osterix, and osteocalcin. The signaling pathways involved in the regulation of OPN and its effect on the periodontal tissues during orthodontic tooth movement are further discussed in this review. A limited number of studies have suggested the use of OPN as a biomarker to assess orthodontic treatment. Furthermore, the association of single nucleotide polymorphisms (SNPs) in OPN coding gene Spp1 with orthodontically induced root resorption remains largely unexplored. Accordingly, future research directions for OPN are outlined in this review.

Highlights

Osteopontin (OPN) is a highly phosphorylated and glycosylated sialoprotein that is expressed by several cell types including osteoblasts, osteocytes, and odontoblasts
Orthodontic forces exert a significant amount of compressive [3–9] and tensional [7, 10–13] forces on the periodontium to induce the signaling pathways mediated by various osteogenic genes including OPN, bone sialoprotein, Osterix, and osteocalcin
OPN-αvβ3 binding on the surface of osteoclasts induces integrin clustering and leads to intracellular signaling by phosphorylation of protein tyrosine kinase 2 (PYK2) [25, 26] that facilitate binding of proto-oncogene tyrosine-protein kinase (Src) via its SH2 domain

Summary

Background

Osteopontin (OPN) is a highly phosphorylated and glycosylated sialoprotein that is expressed by several cell types including osteoblasts, osteocytes, and odontoblasts. OPN binding to αvβ is crucial for major post-receptor signal responses, which involves regulation of osteoclastic activity and activation of osteoprotegerin expression [24, 25]. OPN-αvβ binding on the surface of osteoclasts induces integrin clustering and leads to intracellular signaling by phosphorylation of protein tyrosine kinase 2 (PYK2) [25, 26] that facilitate binding of proto-oncogene tyrosine-protein kinase (Src) via its SH2 domain. This Src-PYK2 binding leads to further phosphorylation of PYK2 at other sites which amplifies the signals activating cellular functions including cell adhesion such as sealing zone formation (Fig. 2b) [25, 26]. Inorganic phosphate [69] Systematic conditions—hypophosphatemia, hypocalcemia [2] Hormones—glucocorticoids, [70] 1,25-dihydroxyvitamin D3, [70] parathyroid hormone [14] Vitamins—retinoic acid [70] Inflammatory mediators—TNFα, IL-1β, TGFβ [14]

Mechanical stress

Conclusions