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Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts.
Bone. 2004 Aug; 35(2):570-6.BONE

Abstract

Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that was first detected in tumor-induced osteomalacia (TIO). Investigations in mice revealed that MEPE is expressed in bone and teeth in a maturation-dependent manner, reaching its maximum during mineralization. However, from knockout experiments, although it has become clear that MEPE might function as a mineralization inhibitor, the exact mechanism of action is still unclear. Even less is known about the regulation of MEPE in men. Therefore, we have studied the time- and maturation-dependent expression of MEPE in two human osteoblast culture systems, the osteosarcoma cell line HOS 58 and primary trabecular osteoblasts. Cells were cultured for up to 29 days, and the influence of beta-glycerophosphate (bGP), ascorbate, transforming growth factor beta (TGF-beta), BMP-2, and dexamethasone was studied. HOS 58 cells showed no significant effect on MEPE gene expression up to 5.0 mM, but a significant inhibition was revealed at 10 and 20 mM, when osteocalcin (OC) expression was maximal. Under the same conditions, primary human osteoblasts showed no effect on MEPE gene expression. However, when cultured in the presence of 5 mM beta-glycerophosphate, ascorbate, and dexamethasone for 29 days, which are similar conditions to those described by Owen in his differentiation model in rat osteoblasts, a progressive inhibition of MEPE gene expression to 20% of the maximum was observed. Increasing osteocalcin expression indicated advancing differentiation. In conclusion, in contrast to the results in mice, when MEPE was maximally expressed during mineralization, in the human system, this factor seems to be maximally active in the proliferation and early matrix maturation phase. It was, however, strongly suppressed, associated with the mineralization phase.

Authors+Show Affiliations

Department of Gastroenterology and Endocrinology, Georg-August-University, Göttingen, Germany. hsiggel@med.uni-goettingen.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

15268910

Citation

Siggelkow, H, et al. "Evidence of Downregulation of Matrix Extracellular Phosphoglycoprotein During Terminal Differentiation in Human Osteoblasts." Bone, vol. 35, no. 2, 2004, pp. 570-6.
Siggelkow H, Schmidt E, Hennies B, et al. Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts. Bone. 2004;35(2):570-6.
Siggelkow, H., Schmidt, E., Hennies, B., & Hüfner, M. (2004). Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts. Bone, 35(2), 570-6.
Siggelkow H, et al. Evidence of Downregulation of Matrix Extracellular Phosphoglycoprotein During Terminal Differentiation in Human Osteoblasts. Bone. 2004;35(2):570-6. PubMed PMID: 15268910.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evidence of downregulation of matrix extracellular phosphoglycoprotein during terminal differentiation in human osteoblasts. AU - Siggelkow,H, AU - Schmidt,E, AU - Hennies,B, AU - Hüfner,M, PY - 2003/12/18/received PY - 2004/03/10/revised PY - 2004/03/30/accepted PY - 2004/7/23/pubmed PY - 2005/2/4/medline PY - 2004/7/23/entrez SP - 570 EP - 6 JF - Bone JO - Bone VL - 35 IS - 2 N2 - Matrix extracellular phosphoglycoprotein (MEPE) is an extracellular matrix protein that was first detected in tumor-induced osteomalacia (TIO). Investigations in mice revealed that MEPE is expressed in bone and teeth in a maturation-dependent manner, reaching its maximum during mineralization. However, from knockout experiments, although it has become clear that MEPE might function as a mineralization inhibitor, the exact mechanism of action is still unclear. Even less is known about the regulation of MEPE in men. Therefore, we have studied the time- and maturation-dependent expression of MEPE in two human osteoblast culture systems, the osteosarcoma cell line HOS 58 and primary trabecular osteoblasts. Cells were cultured for up to 29 days, and the influence of beta-glycerophosphate (bGP), ascorbate, transforming growth factor beta (TGF-beta), BMP-2, and dexamethasone was studied. HOS 58 cells showed no significant effect on MEPE gene expression up to 5.0 mM, but a significant inhibition was revealed at 10 and 20 mM, when osteocalcin (OC) expression was maximal. Under the same conditions, primary human osteoblasts showed no effect on MEPE gene expression. However, when cultured in the presence of 5 mM beta-glycerophosphate, ascorbate, and dexamethasone for 29 days, which are similar conditions to those described by Owen in his differentiation model in rat osteoblasts, a progressive inhibition of MEPE gene expression to 20% of the maximum was observed. Increasing osteocalcin expression indicated advancing differentiation. In conclusion, in contrast to the results in mice, when MEPE was maximally expressed during mineralization, in the human system, this factor seems to be maximally active in the proliferation and early matrix maturation phase. It was, however, strongly suppressed, associated with the mineralization phase. SN - 8756-3282 UR - https://www.unboundmedicine.com/medline/citation/15268910/Evidence_of_downregulation_of_matrix_extracellular_phosphoglycoprotein_during_terminal_differentiation_in_human_osteoblasts_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S875632820400153X DB - PRIME DP - Unbound Medicine ER -