Plasminogen/plasmin modulates bone metabolism by regulating the osteoblast and osteoclast function.
The contribution of plasminogen (Plg)/plasmin, which have claimed to be the main fibrinolytic regulators in the bone metabolism, remains unclear. This study evaluated how the absence of Plg affects the function of osteoblast (OB) and osteoclast (OC). There was a larger population of pre-OCs in bone marrow-derived cells from the Plg(-/-) mice than the population of that from the WT mice. In addition, the absence of Plg suppressed the expression of osteoprotegerin in OBs. Moreover, an exogenous plasmin clearly induced the osteoprotegerin expression in Plg(-/-) OBs. The osteoclastogenesis of RAW264.7 mouse monocyte/macrophage lineage cells in co-culture with OBs from the Plg(-/-) mice was significantly accelerated in comparison with that in co-culture with OBs from the WT mice. Intriguingly, the accelerated OC differentiation of RAW264.7 cells co-cultured with Plg(-/-) OBs was clearly suppressed by the treatment of an exogenous plasmin. Consequently, Plg(-/-) mice display decreased bone mineral density. These findings could eventually lead to the development of new clinical therapies for bone disease caused by a disorder of the fibrinolytic system.
Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's Collage of Liberal Arts, 97-1 Kodo Kyo-tanabe, Kyoto 610-0395, Japan. ykanno@dwc.doshisha.ac.jp
Yosuke
Y
Kanno
Akira
A
Ishisaki
Eri
E
Kawashita
Naoyuki
N
Chosa
Keiichi
K
Nakajima
Tatsuji
T
Nishihara
Kuniaki
K
Toyoshima
Kiyotaka
K
Okada
Shigeru
S
Ueshima
Kenji
K
Matsushita
Osamu
O
Matsuo
Hiroyuki
H
Matsuno
D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001847:Bone Diseases / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005341:Fibrinolysin / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*
D010958:Plasminogen; D005341:Fibrinolysin
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