In vitro bone formation induced by immunosuppressive agent tacrolimus hydrate (FK506).
When rat bone marrow cells were cultured with an immunosuppressive agent, tacrolimus hydrate (FK506), as well as with beta-glycerophosphate and vitamin C, numerous cell clusters became positive for alkaline phosphatase activity. Scanning electron microscopy revealed mineralized bone matrix in the cell clusters, which was identical to that of living bone. High levels of alkaline phosphatase (ALP), indicating osteoblastic activity, and high levels of osteocalcin (Oc) and calcium were found in the mature bone matrix of the cultures. There was significantly increased expression of mRNAs for ALP and Oc. These results indicate that the cultures contained both bone matrix and high osteoblastic activity, suggesting that FK506 induces ossification.
Yoshikawa
Takafumi
T
Department of Orthopedic Surgery, Nara Medical University, Kashihara, Japan. tyoshi@naramed-u.ac.jp
Nakajima
Hiroshi
H
Uemura
Toshimasa
T
Kasai
Takahiko
T
Enomoto
Yasunori
Y
Tamura
Tomomi
T
Nonomura
Akitaka
A
Takakura
Yoshinori
Y
D000818:Animals; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D008297:Male; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D016559:Tacrolimus / Q000008:administration & dosage*; D023822:Tissue Engineering / Q000379:methods*
D007166:Immunosuppressive Agents; D016559:Tacrolimus