PMID- 29694681
OWN - NLM
STAT- MEDLINE
DCOM- 20191024
LR  - 20191024
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Linking)
VI  - 33
IP  - 8
DP  - 2018 Aug
TI  - Annexin A5 Involvement in Bone Overgrowth at the Enthesis.
PG  - 1532-1543
LID - 10.1002/jbmr.3453 [doi]
AB  - 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 wild-type (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.
CI  - (c) 2018 American Society for Bone and Mineral Research.
FAU - Shimada, Akemi
AU  - Shimada A
AD  - Department of Pharmacology, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Ideno, Hisashi
AU  - Ideno H
AD  - Department of Pharmacology, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Arai, Yoshinori
AU  - Arai Y
AD  - Nihon University, School of Dentistry, Chiyoda-ku, Tokyo, Japan.
FAU - Komatsu, Koichiro
AU  - Komatsu K
AD  - Department of Pharmacology, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Wada, Satoshi
AU  - Wada S
AD  - Department of Orthodontics, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Yamashita, Teruhito
AU  - Yamashita T
AD  - Division of Hard Tissue Research, Institute for Oral Science, Matsumoto Dental 
      University, Shiojiri, Japan.
FAU - Amizuka, Norio
AU  - Amizuka N
AD  - Department of Developmental Biology of Hard Tissue, Division of Oral Health 
      Science, Graduate School of Dental Medicine, Hokkaido University, Sapporo, Japan.
FAU - Poschl, Ernst
AU  - Poschl E
AD  - School of Biological Sciences, University of East Anglia, Norwich Research Park, 
      Norwich, UK.
FAU - Brachvogel, Bent
AU  - Brachvogel B
AD  - Experimental Neonatology, Department of Pediatrics and Adolescent Medicine, 
      Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, 
      Germany.
FAU - Nakamura, Yoshiki
AU  - Nakamura Y
AD  - Department of Orthodontics, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Nakashima, Kazuhisa
AU  - Nakashima K
AD  - Department of Pharmacology, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
FAU - Mizukami, Hiroaki
AU  - Mizukami H
AD  - Division of Genetics Therapeutics, Center for Molecular Medicine, Jichi Medical 
      University, Shimotsuke, Japan.
FAU - Ezura, Yoichi
AU  - Ezura Y
AD  - Department of Molecular Pharmacology, Medical Research Institute, Tokyo Medical 
      and Dental University, Bunkyo-ku, Tokyo, Japan.
FAU - Nifuji, Akira
AU  - Nifuji A
AD  - Department of Pharmacology, Tsurumi University School of Dental Medicine, 
      Yokohama, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
RN  - 0 (Annexin A5)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/metabolism
MH  - Animals
MH  - Annexin A5/deficiency/*metabolism
MH  - *Bone Development
MH  - Bone and Bones/*metabolism
MH  - Cartilage/growth & development
MH  - Cell Differentiation
MH  - Chondrocytes/metabolism
MH  - Femur/growth & development/metabolism
MH  - Hindlimb/metabolism
MH  - Mice, Knockout
MH  - Osteoblasts/metabolism
MH  - Tendons/growth & development
MH  - Tenocytes/metabolism
MH  - Tibia/growth & development/metabolism
MH  - Weight-Bearing
OTO - NOTNLM
OT  - ANNEXIN A5
OT  - BONE MORPHOGENESIS
OT  - ENTHESIS
OT  - LACZ KNOCK-IN MOUSE
OT  - TENDON/LIGAMENT
EDAT- 2018/04/26 06:00
MHDA- 2019/10/28 06:00
CRDT- 2018/04/26 06:00
PHST- 2017/08/24 00:00 [received]
PHST- 2018/04/08 00:00 [revised]
PHST- 2018/08/12 00:00 [accepted]
PHST- 2018/04/26 06:00 [pubmed]
PHST- 2019/10/28 06:00 [medline]
PHST- 2018/04/26 06:00 [entrez]
AID - 10.1002/jbmr.3453 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2018 Aug;33(8):1532-1543. doi: 10.1002/jbmr.3453.