The combination of pamidronate and calcitriol reverses particle- and TNF-alpha-induced altered functions of bone-marrow-derived stromal cells with osteoblastic phenotype.
Periprosthetic bone loss after total joint arthroplasty is a major clinical problem resulting in aseptic loosening of the implant. Among many cell types, osteoblasts play a crucial role in the development of peri-implant osteolysis. In this study, we tested the effects of calcitriol (1alpha,25-dihydroxy-vitamin-D3) and the bisphosphonate pamidronate on titanium-particle- and TNF-alpha-induced release of interleukin-6 and suppression of osteoblast-specific gene expressions in bone-marrow-derived stromal cells with an osteoblastic phenotype. We monitored the expression of procollagen alpha1[1], osteocalcin, osteonectin and alkaline phosphatase mRNAs by Northern blots and real-time reverse transcription and polymerase chain reaction analyses. The release of various cytokines was also analysed by ELISA. We found that calcitriol or pamidronate could only partially recover the altered functions of osteoblasts when added alone. Only a combination of these compounds restored all the tested functions of osteoblasts. The local delivery of these drugs may have therapeutic potential to prevent or to treat periprosthetic osteolysis and aseptic loosening of implants.
Vermes
C
C
Rush University Medical Center, Chicago, Illinois 60612, USA.
Chandrasekaran
R
R
Dobai
J G
JG
Jacobs
J J
JJ
Andersson
G B J
GB
An
H
H
Hallab
N J
NJ
Galante
J O
JO
Glant
T T
TT
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D002117:Calcitriol / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D015676:Osteonectin / Q000378:metabolism; D000077268:Pamidronate; D011347:Procollagen / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells; D014025:Titanium / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004164:Diphosphonates; D004338:Drug Combinations; D015850:Interleukin-6; D015676:Osteonectin; D011347:Procollagen; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014025:Titanium; D000469:Alkaline Phosphatase; D002117:Calcitriol; D000077268:Pamidronate