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MEPE is a novel regulator of growth plate cartilage mineralization

MEPE is a novel regulator of growth plate cartilage mineralization
MEPE is a novel regulator of growth plate cartilage mineralization
Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. Although the growth plates of MEPE-overexpressing mice display severe morphological disruption, the expression and function of MEPE in growth plate matrix mineralization remains largely undefined. Here we show MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide, to be localised to the hypertrophic zone of the growth plate. We also demonstrate that the phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. Interestingly, we show that the addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. For a more physiologically relevant model, we utilized the metatarsal organ culture model. We show the pASARM peptide to inhibit mineralization at two stages of development, as shown by histological and ?CT analysis. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. Taken together these results show MEPE to be an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide.
mepe, asarm, growth plate, mineralization, chondrocyte
8756-3282
418-430
Staines, K.A.
74832970-bd61-42fa-84b6-0de5f475377b
Mackenzie, N.C.W.
f8fa17f6-936f-4180-9b6d-59a7a0710517
Clarkin, C.E.
05cd2a88-1127-41aa-a29b-7ac323b4f3c9
Zelenchuk, L.
a85ec599-702d-4c2b-abee-e5cf1f9a2f5d
Rowe, P.S.
0b843eb9-c240-4bc8-aecd-6c913a7cf96c
MacRae, V.E.
cfd5510d-0caa-4651-b17c-f074756ab691
Farquharson, C.
8d83ca84-0188-4a36-98c7-750d37d53601
Staines, K.A.
74832970-bd61-42fa-84b6-0de5f475377b
Mackenzie, N.C.W.
f8fa17f6-936f-4180-9b6d-59a7a0710517
Clarkin, C.E.
05cd2a88-1127-41aa-a29b-7ac323b4f3c9
Zelenchuk, L.
a85ec599-702d-4c2b-abee-e5cf1f9a2f5d
Rowe, P.S.
0b843eb9-c240-4bc8-aecd-6c913a7cf96c
MacRae, V.E.
cfd5510d-0caa-4651-b17c-f074756ab691
Farquharson, C.
8d83ca84-0188-4a36-98c7-750d37d53601

Staines, K.A., Mackenzie, N.C.W., Clarkin, C.E., Zelenchuk, L., Rowe, P.S., MacRae, V.E. and Farquharson, C. (2012) MEPE is a novel regulator of growth plate cartilage mineralization. Bone, 51 (3), 418-430. (doi:10.1016/j.bone.2012.06.022). (PMID:22766095)

Record type: Article

Abstract

Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. Although the growth plates of MEPE-overexpressing mice display severe morphological disruption, the expression and function of MEPE in growth plate matrix mineralization remains largely undefined. Here we show MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide, to be localised to the hypertrophic zone of the growth plate. We also demonstrate that the phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. Interestingly, we show that the addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. For a more physiologically relevant model, we utilized the metatarsal organ culture model. We show the pASARM peptide to inhibit mineralization at two stages of development, as shown by histological and ?CT analysis. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. Taken together these results show MEPE to be an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide.

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More information

e-pub ahead of print date: 6 July 2012
Published date: September 2012
Keywords: mepe, asarm, growth plate, mineralization, chondrocyte
Organisations: Biomedicine

Identifiers

Local EPrints ID: 341959
URI: http://eprints.soton.ac.uk/id/eprint/341959
ISSN: 8756-3282
PURE UUID: d625eb02-4383-4f11-928e-ed464ed06ec4

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Date deposited: 09 Aug 2012 08:49
Last modified: 16 Jul 2019 21:56

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