Inhibition of Midkine Augments Osteoporotic Fracture Healing
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Inhibition of Midkine Augments Osteoporotic Fracture Healing. / Haffner-Luntzer, Melanie; Kemmler, Julia; Heidler, Verena; Prystaz, Katja; Schinke, Thorsten; Amling, Michael; Kovtun, Anna; Rapp, Anna E; Ignatius, Anita; Liedert, Astrid.
In: PLOS ONE, Vol. 11, No. 7, 2016, p. e0159278.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Inhibition of Midkine Augments Osteoporotic Fracture Healing
AU - Haffner-Luntzer, Melanie
AU - Kemmler, Julia
AU - Heidler, Verena
AU - Prystaz, Katja
AU - Schinke, Thorsten
AU - Amling, Michael
AU - Kovtun, Anna
AU - Rapp, Anna E
AU - Ignatius, Anita
AU - Liedert, Astrid
PY - 2016
Y1 - 2016
N2 - The heparin-binding growth and differentiation factor midkine (Mdk) is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX)-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab) improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications.
AB - The heparin-binding growth and differentiation factor midkine (Mdk) is proposed to negatively regulate osteoblast activity and bone formation in the adult skeleton. As Mdk-deficient mice were protected from ovariectomy (OVX)-induced bone loss, this factor may also play a role in the pathogenesis of postmenopausal osteoporosis. We have previously demonstrated that Mdk negatively influences bone regeneration during fracture healing. Here, we investigated whether the inhibition of Mdk using an Mdk-antibody (Mdk-Ab) improves compromised bone healing in osteoporotic OVX-mice. Using a standardized femur osteotomy model, we demonstrated that Mdk serum levels were significantly enhanced after fracture in both non-OVX and OVX-mice, however, the increase was considerably greater in osteoporotic mice. Systemic treatment with the Mdk-Ab significantly improved bone healing in osteoporotic mice by increasing bone formation in the fracture callus. On the molecular level, we demonstrated that the OVX-induced reduction of the osteoanabolic beta-catenin signaling in the bony callus was abolished by Mdk-Ab treatment. Furthermore, the injection of the Mdk-Ab increased trabecular bone mass in the skeleton of the osteoporotic mice. These results implicate that antagonizing Mdk may be useful for the therapy of osteoporosis and osteoporotic fracture-healing complications.
KW - Journal Article
U2 - 10.1371/journal.pone.0159278
DO - 10.1371/journal.pone.0159278
M3 - SCORING: Journal article
C2 - 27410432
VL - 11
SP - e0159278
JO - PLOS ONE
JF - PLOS ONE
SN - 1932-6203
IS - 7
ER -
