Universität zu Köln

Shimada, Akemi, Ideno, Hisashi, Arai, Yoshinori, Komatsu, Koichiro, Wada, Satoshi, Yamashita, Teruhito, Amizuka, Norio, Poschl, Ernst, Brachvogel, Bent, Nakamura, Yoshiki, Nakashima, Kazuhisa ORCID: 0000-0003-0491-2149, Mizukami, Hiroaki ORCID: 0000-0001-8954-874X, Ezura, Yoichi and Nifuji, Akira ORCID: 0000-0002-8182-4380 (2018). Annexin A5 Involvement in Bone Overgrowth at the Enthesis. J. Bone Miner. Res., 33 (8). S. 1532 - 1544. HOBOKEN: WILEY. ISSN 1523-4681

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Abstract

Little is known about the molecular mechanisms of enthesis formation in mature animals. Here, we report that annexin A5 (Anxa5) plays a critical role in the regulation of bone ridge outgrowth at the entheses. We found that Anxa5 is highly expressed in the entheses of postnatal and adult mice. In Anxa5-deficient (Anxa5(-/-)) mice, the sizes of bone ridge outgrowths at the entheses of the tibias and femur were increased after age 7 weeks. Bone overgrowth was not observed at the fibrous enthesis where the fibrocartilage layer does not exist. More ALP-expressing cells were observed in the fibrocartilage layer in Anxa5(-/-) mice than in wildtype (WT) mice. Calcein and Alizarin Red double labeling revealed more mineralized areas in Anxa5(-/-) mice than WT mice. To examine the effects of mechanical forces, we performed tenotomy in which transmission of contractile forces by the tibial muscle was impaired by surgical muscle release. In tenotomized mice, bone overgrowth at the enthesis in Anxa5(-/-) mice was decreased to a level comparable to that in WT mice at 8 weeks after the operation. The tail-suspended mice also showed a decrease in bone overgrowth to similar levels in Anxa5(-/-) and WT mice at 8 weeks after hindlimb unloading. These results suggest that bone overgrowth at the enthesis requires mechanical forces. We further examined effects of Anxa5 gene knockdown (KD) in primary cultures of osteoblasts, chondrocytes, and tenocytes in vitro. Anxa5 KD increased ALP expression in tenocytes and chondrocytes but not in osteoblasts, suggesting that increased ALP activity in the fibrocartilaginous tissue in Anxa5(-/-) mice is directly caused by Anxa5 deletion in tenocytes or fibrocartilage cells. These data indicate that Anxa5 prevents bone overgrowth at the enthesis, whose formation is mediated through mechanical forces and modulating expression of mineralization regulators. (c) 2018 American Society for Bone and Mineral Research.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Shimada, Akemi UNSPECIFIED UNSPECIFIED UNSPECIFIED Ideno, Hisashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Arai, Yoshinori UNSPECIFIED UNSPECIFIED UNSPECIFIED Komatsu, Koichiro UNSPECIFIED UNSPECIFIED UNSPECIFIED Wada, Satoshi UNSPECIFIED UNSPECIFIED UNSPECIFIED Yamashita, Teruhito UNSPECIFIED UNSPECIFIED UNSPECIFIED Amizuka, Norio UNSPECIFIED UNSPECIFIED UNSPECIFIED Poschl, Ernst UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakamura, Yoshiki UNSPECIFIED UNSPECIFIED UNSPECIFIED Nakashima, Kazuhisa UNSPECIFIED orcid.org/0000-0003-0491-2149 UNSPECIFIED Mizukami, Hiroaki UNSPECIFIED orcid.org/0000-0001-8954-874X UNSPECIFIED Ezura, Yoichi UNSPECIFIED UNSPECIFIED UNSPECIFIED Nifuji, Akira UNSPECIFIED orcid.org/0000-0002-8182-4380 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-178270
DOI:	10.1002/jbmr.3453
Journal or Publication Title:	J. Bone Miner. Res.
Volume:	33
Number:	8
Page Range:	S. 1532 - 1544
Date:	2018
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1523-4681
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language FUNCTIONAL TENDON ENTHESIS; GROWTH-PLATE CARTILAGE; OSTEOBLASTIC DIFFERENTIATION; FIBROCARTILAGE CELLS; MINERALIZATION; EXPRESSION; PROGENITORS; INSERTION; JUNCTION; COLLAGEN Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17827