A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
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A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts. / Henriksen, Kim; Andreassen, Kim V; Thudium, Christian S; Gudmann, Karoline Natasja Stæhr; Moscatelli, Ilana; Crüger-Hansen, Catherine E; Schulz, Ansgar S; Dziegiel, Morten Hanefeld; Richter, Johan; Karsdal, Morten A; Neutzsky-Wulff, Anita V.
In: The Bone, Vol. 51, No. 3, 09.2012, p. 353-61.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
AU - Henriksen, Kim
AU - Andreassen, Kim V
AU - Thudium, Christian S
AU - Gudmann, Karoline Natasja Stæhr
AU - Moscatelli, Ilana
AU - Crüger-Hansen, Catherine E
AU - Schulz, Ansgar S
AU - Dziegiel, Morten Hanefeld
AU - Richter, Johan
AU - Karsdal, Morten A
AU - Neutzsky-Wulff, Anita V
N1 - Copyright © 2012 Elsevier Inc. All rights reserved.
PY - 2012/9
Y1 - 2012/9
N2 - Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was collected from macrophages, pre-osteoclasts, and mature functional or non-resorbing osteopetrotic osteoclasts on either bone, plastic, decalcified bone or dentine with or without diphyllin, E64 or GM6001. Osteoclasts numbers were measured by TRACP activity. Bone resorption was evaluated by CTX-I and calcium release. The osteoblastic cell line 2T3 was treated with 50% of CM or non-CM for 12days. Bone formation was assessed by Alizarin Red extraction. CM from mature osteoclasts induced bone formation, while CM from macrophages did not. Non-resorbing osteoclasts generated from osteopetrosis patients showed little resorption, but still an induction of bone formation by osteoblasts. Mimicking the reduction in bone resorption using the V-ATPase inhibitor Diphyllin, the cysteine proteinase inhibitor E64 and the MMP-inhibitor GM6001 showed that CM from diphyllin and E64 treated osteoclasts showed reduced ability to induce bone formation compared to CM from vehicle treated osteoclasts, while CM from GM6001 treated osteoclasts equaled vehicle CM. Osteoclasts on either dentine or decalcified bone showed strongly attenuated anabolic capacities. In conclusion, we present evidence that osteoclasts, both dependent and independent of their resorptive activity, secrete factors stimulating osteoblastic bone formation.
AB - Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was collected from macrophages, pre-osteoclasts, and mature functional or non-resorbing osteopetrotic osteoclasts on either bone, plastic, decalcified bone or dentine with or without diphyllin, E64 or GM6001. Osteoclasts numbers were measured by TRACP activity. Bone resorption was evaluated by CTX-I and calcium release. The osteoblastic cell line 2T3 was treated with 50% of CM or non-CM for 12days. Bone formation was assessed by Alizarin Red extraction. CM from mature osteoclasts induced bone formation, while CM from macrophages did not. Non-resorbing osteoclasts generated from osteopetrosis patients showed little resorption, but still an induction of bone formation by osteoblasts. Mimicking the reduction in bone resorption using the V-ATPase inhibitor Diphyllin, the cysteine proteinase inhibitor E64 and the MMP-inhibitor GM6001 showed that CM from diphyllin and E64 treated osteoclasts showed reduced ability to induce bone formation compared to CM from vehicle treated osteoclasts, while CM from GM6001 treated osteoclasts equaled vehicle CM. Osteoclasts on either dentine or decalcified bone showed strongly attenuated anabolic capacities. In conclusion, we present evidence that osteoclasts, both dependent and independent of their resorptive activity, secrete factors stimulating osteoblastic bone formation.
KW - Bone Density Conservation Agents
KW - Bone Matrix
KW - Bone Resorption
KW - Bone and Bones
KW - Cell Differentiation
KW - Cells, Cultured
KW - Dentin
KW - Humans
KW - Osteoblasts
KW - Osteoclasts
KW - Osteogenesis
KW - Time Factors
U2 - 10.1016/j.bone.2012.06.007
DO - 10.1016/j.bone.2012.06.007
M3 - Journal article
C2 - 22722081
VL - 51
SP - 353
EP - 361
JO - The Bone
JF - The Bone
SN - 0914-7047
IS - 3
ER -
ID: 47555092