Dataset Information

Distinct Expression Patterns of Osteopontin and Dentin Matrix Protein 1 Genes in Pituitary Gonadotrophs.

ABSTRACT: Cell-matrix interactions play important roles in pituitary development, physiology, and pathogenesis. In other tissues, a family of non-collagenous proteins, termed SIBLINGs, are known to contribute to cell-matrix interactions. Anterior pituitary gland expresses two SIBLING genes, Dmp1 (dentin matrix protein-1) and Spp1 (secreted phosphoprotein-1) encoding DMP1 and osteopontin proteins, respectively, but their expression pattern and roles in pituitary functions have not been clarified. Here we provide novel evidence supporting the conclusion that Spp1/osteopontin, like Dmp1/DMP1, are expressed in gonadotrophs in a sex- and age-specific manner. Other anterior pituitary cell types do not express these genes. In contrast to Dmp1, Spp1 expression is higher in males; in females, the expression reaches the peak during the diestrus phase of estrous cycle. In further contrast to Dmp1 and marker genes for gonadotrophs, the expression of Spp1 is not regulated by gonadotropin-releasing hormone in vivo and in vitro. However, Spp1 expression increases progressively after pituitary cell dispersion in both female and male cultures. We may speculate that gonadotrophs signal to other pituitary cell types about changes in the structure of pituitary cell-matrix network by osteopontin, a function consistent with the role of this secretory protein in postnatal tissue remodeling, extracellular matrix reorganization after injury, and tumorigenesis.

SUBMITTER: Bjelobaba I

PROVIDER: S-EPMC6478748 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Distinct Expression Patterns of Osteopontin and Dentin Matrix Protein 1 Genes in Pituitary Gonadotrophs.

Bjelobaba Ivana I Janjic Marija M MM Prévide Rafael Maso RM Abebe Daniel D Kucka Marek M Stojilkovic Stanko S SS

Frontiers in endocrinology 20190417

Cell-matrix interactions play important roles in pituitary development, physiology, and pathogenesis. In other tissues, a family of non-collagenous proteins, termed SIBLINGs, are known to contribute to cell-matrix interactions. Anterior pituitary gland expresses two SIBLING genes, <i>Dmp1</i> (dentin matrix protein-1) and <i>Spp1</i> (secreted phosphoprotein-1) encoding DMP1 and osteopontin proteins, respectively, but their expression pattern and roles in pituitary functions have not been clarif ...[more]

PMID: 31057484

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Project description:The SIBLINGs are a subfamily of the secreted calcium-binding phosphoproteins and comprise five small integrin-binding ligand N-linked glycoproteins [dentin matrix protein-1 (DMP1), secreted phosphoprotein-1 (SPP1) also called osteopontin (OPN), integrin-binding sialoprotein (IBSP) also called bone sialoprotein (BSP), matrix extracellular phosphoglycoprotein (MEPE), and dentin sialophosphoprotein (DSPP)]. Each SIBLING has at least one "acidic, serine- and aspartic acid-rich motif" (ASARM) and multiple Ser-x-Glu/pSer sequences that when phosphorylated promote binding of the protein to hydroxyapatite for regulation of biomineralization. Mendelian disorders from loss-of-function mutation(s) of the genes that encode the SIBLINGs thus far involve DSPP causing various autosomal dominant dysplasias of dentin but without skeletal disease, and DMP1 causing autosomal recessive hypophosphatemic rickets, type 1 (ARHR1). No diseases have been reported from gain-of-function mutation(s) of DSPP or DMP1 or from alterations of SPP1, IBSP, or MEPE. Herein, we describe severe hypophosphatemic osteosclerosis and hyperostosis associated with skeletal deformity, short stature, enthesopathy, tooth loss, and high circulating FGF23 levels in a middle-aged man and young woman from an endogamous family living in southern India. Both shared novel homozygous mutations within two genes that encode a SIBLING protein: stop-gain ("nonsense") DMP1 (c.556G>T,p.Glu186Ter) and missense SPP1 (c.769C>T,p.Leu266Phe). The man alone also carried novel heterozygous missense variants within two additional genes that condition mineral homeostasis and are the basis for autosomal recessive disorders: CYP27B1 underlying vitamin D dependent rickets, type 1, and ABCC6 underlying both generalized arterial calcification of infancy, type 2 and pseudoxanthoma elasticum (PXE). By immunochemistry, his bone contained high amounts of OPN, particularly striking surrounding osteocytes. We review how our patients' disorder may represent the first digenic SIBLING protein osteopathy.

Project description:The periodontal complex is essential for tooth attachment and function and includes the mineralized tissues, cementum and alveolar bone, separated by the unmineralized periodontal ligament (PDL). To gain insights into factors regulating cementum-PDL and bone-PDL borders and protecting against ectopic calcification within the PDL, we employed a proteomic approach to analyze PDL tissue from progressive ankylosis knock-out (Ank-/-) mice, featuring reduced PPi, rapid cementogenesis, and excessive acellular cementum. Using this approach, we identified the matrix protein osteopontin (Spp1/OPN) as an elevated factor of interest in Ank-/- mouse molar PDL. We studied the role of OPN in dental and periodontal development and function. During tooth development in wild-type (WT) mice, Spp1 mRNA was transiently expressed by cementoblasts and strongly by alveolar bone osteoblasts. Developmental analysis from 14 to 240days postnatal (dpn) indicated normal histological structures in Spp1-/- comparable to WT control mice. Microcomputed tomography (micro-CT) analysis at 30 and 90dpn revealed significantly increased volumes and tissue mineral densities of Spp1-/- mouse dentin and alveolar bone, while pulp and PDL volumes were decreased and tissue densities were increased. However, acellular cementum growth was unaltered in Spp1-/- mice. Quantitative PCR of periodontal-derived mRNA failed to identify potential local compensators influencing cementum in Spp1-/- vs. WT mice at 26dpn. We genetically deleted Spp1 on the Ank-/- mouse background to determine whether increased Spp1/OPN was regulating periodontal tissues when the PDL space is challenged by hypercementosis in Ank-/- mice. Ank-/-; Spp1-/- double deficient mice did not exhibit greater hypercementosis than that in Ank-/- mice. Based on these data, we conclude that OPN has a non-redundant role regulating formation and mineralization of dentin and bone, influences tissue properties of PDL and pulp, but does not control acellular cementum apposition. These findings may inform therapies targeted at controlling soft tissue calcification.

Dataset Information

Distinct Expression Patterns of Osteopontin and Dentin Matrix Protein 1 Genes in Pituitary Gonadotrophs.

Publications

Distinct Expression Patterns of Osteopontin and Dentin Matrix Protein 1 Genes in Pituitary Gonadotrophs.

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