Osteoprotegerin and receptor activator of nuclear factor kappaB ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint.
OBJECTIVE
This study investigated the involvement of the recently identified regulators of osteoclast formation RANKL [receptor activator of nuclear factor kappaB (RANK) ligand, osteoclast differentiation factor, TRANCE, osteoprotegerin ligand] and its natural inhibitor, osteoprotegerin (OPG), in the bone erosion of rheumatoid arthritis (RA).


METHODS
mRNA was extracted from cells isolated from the pannus and synovial membrane regions of joints of 11 RA patients. Semiquantitative reverse transcription-polymerase chain reaction was carried out, and the isolated cells were also cultured to determine their ability to form osteoclasts.


RESULTS
mRNAs encoding RANKL, RANK, OPG and macrophage-colony stimulating factor were expressed by cells isolated from RA joints. In addition, mRNA encoding for tumour necrosis factor apoptosis-inducing ligand and the osteoclast markers tartrate-resistant acid phosphatase and calcitonin receptor were also often expressed. Osteoclasts capable of forming resorption lacunae were generated from cells in the RA joints. At 50 ng/ml, recombinant OPG completely inhibited the resorptive activity of these cells. There was a significant correlation between the ratio of RANKL mRNA to OPG mRNA and the number of resorption pits produced (P = 0.028).


CONCLUSIONS
These data suggest that RANKL is an essential factor for osteoclast formation by cells in the rheumatic joint and that OPG may prevent the bone erosion seen in RA joints.
Haynes
D R
DR
Department of Pathology and. Department of Orthopaedics and Trauma, The University of Adelaide and The Royal Adelaide Hospital, Adelaide 5000, SA, Australia.
Crotti
T N
TN
Loric
M
M
Bain
G I
GI
Atkins
G J
GJ
Findlay
D M
DM
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D008875:Middle Aged; D010010:Osteoclasts / Q000502:physiology*; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human