Post-translational modifications of SIBLING proteins and their roles in osteogenesis and dentinogenesis

The Department of Endodontics and Periodontics, University of Texas-Houston Health Science Center, Dental Branch, Houston, TX 77030, USA.
Critical reviews in oral biology and medicine: an official publication of the American Association of Oral Biologists 02/2004; 15(3):126-36. DOI: 10.1177/154411130401500302
Source: PubMed


The extracellular matrix (ECM) of bone and dentin contains several non-collagenous proteins. One category of non-collagenous protein is termed the SIBLING (Small Integrin-Binding LIgand, N-linked Glycoprotein) family, that includes osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoglycoprotein (MEPE). These polyanionic SIBLING proteins are believed to play key biological roles in the mineralization of bone and dentin. Although the specific mechanisms involved in controlling bone and dentin formation are still unknown, it is clear that some functions of the SIBLING family members are dependent on the nature and extent of post-translational modifications (PTMs), such as phosphorylation, glycosylation, and proteolytic processing, since these PTMs would have significant effects on their structure. OPN and BSP are present in the ECM of bone and dentin as full-length forms, whereas amino acid sequencing indicates that DMP1 and DSPP exist as proteolytically processed fragments that result from scission of X-Asp bonds. We hypothesized that the processing of DMP1 and DSPP is catalyzed by the PHEX enzyme, since this protein, an endopeptidase that is predominantly expressed in bone and tooth, has a strong preference for cleavage at the NH2-terminus of aspartyl residue. We envision that the proteolytic processing of DMP1 and DSPP may be an activation process that plays a significant, crucial role in osteogenesis and dentinogenesis, and that a failure in this processing would cause defective mineralization in bone and dentin, as observed in X-linked hypophosphatemic rickets.

Download full-text


Available from: Chunlin Qin, Nov 04, 2014
  • Source
    • "DMP1, also called AG1 in the early literature, is an acidic non collagenous phosphoprotein originally found in teeth (George et al., 1993), but later also detected in bones (Hirst et al., 1997; MacDougall et al., 1998), where it is primarily expressed by osteocytes (Toyosawa et al., 2001). DMP1 is a multifunctional protein involved in the biomineralization of bones and dentin (Ling et al., 2005; Lu et al., 2007; Qin et al., 2004), phosphate homeostasis (Feng et al., 2006), and differentiation of odonto-and osteoblasts (Almushayt et al., 2006; Narayanan et al., 2001). Mutations in this gene cause autosomal recessive hypophosphatemic rickets syndrome , manifested by rickets and osteomalacia with isolated renal phosphate-wasting (Feng et al., 2006; Lorenz-Depiereux et al., 2006). "

  • Source
    • "Longitudinal bone growth is primarily achieved through the action of chondrocytes in the proliferative and proliferative zones of the growth plate [3]. Apart from the effects of circulating systemic and local hormones, calcium and other chemicals, which are mainly provided by bone to maintain the intra-and extracellular mineral pools, can work in cohort with osteoblasts, osteocytes, and extracellular matrix proteins to mineralize osteoid [4]. Calcium is crucial for normal epiphyseal growth plate development, and changes in extracellular calcium modulate the function of chondrocytes [5]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: This study investigated whether long-term treatment with antiepileptic drugs (AEDs) had negative effects on statural growth and serum calcium levels in children with epilepsy in Taiwan. Children with epilepsy treated with one prescription of AEDs (monotherapy) for at least 1 year were selected. The AEDs included valproic acid (VPA; Deparkin) in 27 children (11 boys and 16 girls) aged 4-18 years, oxcarbazepine (Trileptal) in 30 children (15 boys and 15 girls) aged 5-18 years, topiramate (Topamax) in 19 children (10 boys and 9 girls) aged 6-18 years, and lamotrigine (Lamicta) in eight children (5 boys and 3 girls) aged 5-13 years. Patients with a history of febrile convulsions were selected as the controls. One year of VPA treatment significantly impaired the statural growth of pediatric patients with epilepsy (p < 0.005) compared with the control group. The underlying mechanism may have been due to the direct effect of VPA on the proliferation of growth plate chondrocytes rather than alterations of serum calcium. These results raise serious concerns about the growth of pediatric epilepsy patients who use AEDs, and potentially the need to closely monitor growth in children with epilepsy and adolescents under AED treatment, especially VPA.
    BMC Pediatrics 12/2013; 13(1):211. DOI:10.1186/1471-2431-13-211 · 1.93 Impact Factor
  • Source
    • "The importance of NCPs in the mineralization process has been well demonstrated by mutation studies and by experimental suppression of NCP genes. These experiments have highlighted the importance in the mineralization process of SIBLINGs (Small Integrin Binding LIgand N-linked Glycoproteins), a phosphoprotein family in which mutations are associated with abnormal phenotypes in the mineralization of bone and/or dentin (Qin et al., 2004; Opsahl Vital et al., 2012). This family includes dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein (BSP), matrix extracellular phosphorylated glycoprotein (MEPE), and osteopontin (OPN). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Bacterial enzymes have long been considered solely accountable for the degradation of the dentin matrix during the carious process. However, the emerging literature suggests that host-derived enzymes, and in particular the matrix metalloproteinases (MMPs) contained in dentin and saliva can play a major role in this process by their ability to degrade the dentin matrix from within. These findings are important since they open new therapeutic options for caries prevention and treatment. The possibility of using MMP inhibitors to interfere with dentin caries progression is discussed. Furthermore, the potential release of bioactive peptides by the enzymatic cleavage of dentin matrix proteins by MMPs during the carious process is discussed. These peptides, once identified, may constitute promising therapeutical tools for tooth and bone regeneration.
    Frontiers in Physiology 11/2013; 4:308. DOI:10.3389/fphys.2013.00308 · 3.53 Impact Factor
Show more