Evidence of ectokinase-mediated phosphorylation of osteopontin and bone sialoprotein by osteoblasts during bone formation <i>in vitro</i>

Zhu, Xinli; Luo, Chun; Ferrier, Jack; Sodek, Jaro

doi:10.1042/bj3230637

Cited by 42 publications

(24 citation statements)

References 48 publications

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“…Thus, this molecule (ASARM peptide) would predictably sequester free calcium with high avidity and like bisphosphonates inhibit mineralization at high doses [9,46,89]. Moreover, casein kinase II is present in osteoblasts as an ectokinase and phosphorylates extracellular matrix proteins [95,106].…”

Section: Discussionmentioning

confidence: 99%

MEPE has the properties of an osteoblastic phosphatonin and minhibin

Rowe

Kumagai²,

Gutiérrez³

et al. 2004

Bone

246

277

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Matrix extracellular phosphoglycoprotein (MEPE) is expressed exclusively in osteoblasts, osteocytes and odontoblasts with markedly elevated expression found in X-linked hypophosphatemic rickets (Hyp) osteoblasts and in oncogenic hypophosphatemic osteomalacia (OHO) tumors. Because these syndromes are associated with abnormalities in mineralization and renal phosphate excretion, we examined the effects of insect-expressed full-length human-MEPE (Hu-MEPE) on serum and urinary phosphate in vivo, 33 PO 4 uptake in renal proximal tubule cultures and mineralization of osteoblast cultures. Dose-dependent hypophosphatemia and hyperphosphaturia occurred in mice following intraperitoneal (IP) administration of Hu-MEPE (up to 400 μg kg -1 31 h -1 ), similar to mice given the phosphaturic hormone PTH (80 μg kg -1 31 h -1 ). Also the fractional excretion of phosphate (FEP) was stimulated by MEPE [65.0% (P < 0.001)] and PTH groups [53.3% (P < 0.001)] relative to the vehicle group [28.7% (SEM 3.97)]. In addition, Hu-MEPE significantly inhibited 33 PO 4 uptake in primary human proximal tubule renal cells (RPTEC) and a human renal cell line (Hu-CL8) in vitro (V max 53.4% inhibition; K m 27.4 ng/ ml, and V max 9.1% inhibition; K m 23.8 ng/ml, respectively). Moreover, Hu-MEPE dose dependently (50-800 ng/ml) inhibited BMP2-mediated mineralization of a murine osteoblast cell line (2T3) in vitro. Inhibition of mineralization was localized to a small (2 kDa) cathepsin B released carboxy-terminal MEPE peptide (protease-resistant) containing the acidic serineaspartate-rich motif (ASARM peptide). We conclude that MEPE promotes renal phosphate excretion and modulates mineralization.

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Section: Discussionmentioning

confidence: 99%

MEPE has the properties of an osteoblastic phosphatonin and minhibin

Rowe

Kumagai²,

Gutiérrez³

et al. 2004

Bone

246

277

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“…The canalicular space is a site where mineral ions are exchanged between bone and extracellular fluid in the processes of resorption and mineralization of the organic matrix (39). The canalicular space is also a site for extracellular phosphorylation of matrix proteins that bind mineral ions (40,41). Reduced canalicular number/density in the long bones of Mmp2 Ϫ/Ϫ mice could result in decreased surface area and, ultimately, decreased secondary mineralization (22,23).…”

Section: Mmp2mentioning

confidence: 99%

A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

Inoue

Mikuni-Takagaki

Oikawa

et al. 2006

Journal of Biological Chemistry

179

171

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Bone is continuously remodeled to adopt a volume appropriate for the local environment; the amount of bone deposited depends on the balance between bone formation and resorption by bone cells, osteoblasts, osteoclasts, and osteocytes (1). Osteoblasts are bone-forming cells that differentiate from mesenchymal stem cells and secrete extracellular matrix (ECM) 4 proteins, which are subsequently mineralized. Osteoclasts are bone-resorbing cells that differentiate from hematopoietic stem cells and degrade bone ECM proteins after demineralization in the extracellular space (Howship's lacunae) adjacent to the ruffled borders. In contrast to osteoblasts and osteoclasts, which act at bone surfaces, osteocytes, cells of osteoblastic lineage, are embedded in bone and are terminally differentiated. Osteocytes extend their dendritic processes into the bone matrix to constitute a well developed canalicular network with other cells. Although osteocytes are the most abundant cell type in bone tissue, their role in bone metabolism is not firmly established.ECM production and degradation by bone cells are critical steps in bone metabolism (1), and disturbed ECM turnover leads to bone disease. Type I collagen is a major ECM component. Secreted type I collagen molecules are processed by propeptidases and cross-linked by lysyl oxidases into mature collagen. Mutations of genes encoding type I collagen cause the bone disease osteogenesis imperfecta (2). Type I collagens are mainly degraded by matrix metalloproteinases (MMPs), which exert their enzymatic activity at a neutral pH in a zinc ion-dependent manner (3, 4). Several MMPs are expressed in bone tissue (5-9). MMPs may play a role in osteoclastic bone resorption (4, 5). Osteoblasts and osteocytes also produce MMPs such as MMP-2 and MMP-13 (7-9). Recent linkage analysis suggests that a loss of function mutation of MMP2 causes a human autosomal recessive disorder with multicentric nodulosis, arthropathy with joint erosion, and osteolysis, termed NAO syndrome (10, 11). This syndrome also includes facial abnormalities and generalized * This work was supported in part by a grant from the Ministry for Welfare and Health of Japan (to S. I.), by a Sasagawa Scientific Research Grant from the Japan Science Society (to K. I.), by a grant from the Japan Space Forum, National Space Development Agency of Japan (NASDA) (to N. M.), and by a research grant from the National Institutes of Health (to S. M. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. 4 The abbreviations used are: ECM, extracellular matrix; DMP-1, dentin matrix protein 1; DMEM, Dulbecco's modified Eagle's medium; MMP, matrix metalloproteinase; NAO, nodulosis, arthropathy, and osteolysis; BMD, bone mineral density; pQCT, peripheral quantitative computed tomography; MAR, mineral apposition rate; BFR/BS, ratio of bone formation rate to bone surface.

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“…Phosphorylation of proteins located at the cell surface has been reported in many types of cells, including platelets [24,25], monocytes [26], osteoblasts [27], vascular smooth space can be applied, and they are applicable at any places even where endogenous PKs are not functional. Therefore, responses that endogenous ecto-PKs do not evoke can be expected.…”

Section: Extracellular Phosphorylationmentioning

confidence: 99%

Ecto-Phosphorylation and Regeneration of the Adult Central Nervous System

Takei¹,

Amagase²

2017

Protein Phosphorylation

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Phosphorylation of ecto-domains of membrane proteins and extracellular matrix proteins, which is termed ecto-phosphorylation, activates intracellular signalling and has roles in several physiological processes including cell adhesion, fertilisation and fibrinolysis. We demonstrated that ecto-phosphorylation can promote endogenous neurogenesis in the damaged central nervous system (CNS), augmenting its functional recovery. Thus, regulation of ecto-phosphorylation could be a platform for development of therapeutic methods against CNS injury. Regeneration of the damaged CNS is long-awaited. While transplantation of neuronal progenitor cells is expected to be the first platform to develop the therapy, the potential of endogenous neurogenesis as a source of new neurons has been expected to be an inexpensive and non-invasive regenerative medicine for CNS injury. In this review, we focused on the spinal cord as a model of CNS recovery from traumatic injury. The spinal cord is the simplest part of the CNS and its function is well known. Therefore, estimation of recovery is easier than other part of the CNS. Firstly, we introduce endogenous neural stem cells (NSCs) in the adult spinal cord and their behaviour after injury and then discuss effects of ecto-phosphorylation, which induces regeneration of the adult spinal cord.

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Evidence of ectokinase-mediated phosphorylation of osteopontin and bone sialoprotein by osteoblasts during bone formation in vitro

Abstract: Osteopontin (OPN) and bone sialoprotein (BSP) are phosphorylated glycoproteins that, together with osteonectin\ secreted protein, acidic, rich in cysteine (SPARC) and osteocalcin, comprise the major non-collagen proteins of bone.

Cited by 42 publications

References 48 publications

MEPE has the properties of an osteoblastic phosphatonin and minhibin

MEPE has the properties of an osteoblastic phosphatonin and minhibin

A Crucial Role for Matrix Metalloproteinase 2 in Osteocytic Canalicular Formation and Bone Metabolism

Ecto-Phosphorylation and Regeneration of the Adult Central Nervous System

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