Increased Dickkopf-1 expression accelerates bone cell apoptosis in femoral head osteonecrosis.
Intensive bone cell apoptosis contributes to osteonecrosis of femoral head (ONFH). Dickkopf-1 (DKK1) reportedly mediates various types of skeletal disorders. This study investigated whether DKK1 was linked to the occurrence of ONFH. Thirty-nine patients with various stages of ONFH were recruited. Bone specimens were harvested from 34 ONFH patients underwent hip arthroplasty, and from 10 femoral neck fracture patients. Bad, Bcl2 TNFalpha, DKK1, Wnt3a, LRP5, and Axin1 expressions were analyzed by quantitative RT-PCR and ELISA. Apoptotic cells were assayed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labelling (TUNEL). Primary bone-marrow mesenchymal cells were treated with DKK1 RNA interference and recombinant DKK1 protein. ONFH patients with the histories of being administrated corticosteroids and excessive alcohol consumption had significantly higher Bad and DKK1 mRNA expressions in bone tissue and DKK1 abundances in serum than femoral neck fracture patients. Bone cells adjacent to osteonecrotic bone displayed strong DKK1 immunoreactivity and TUNEL staining. Increased DKK1 expression in bone tissue and serum correlated with Bad expression and TUNEL staining. Serum DKK1 abundance correlated with the severity of ONFH. The DKK1 RNA interference and recombinant DKK1 protein regulated Bad expression and apoptosis of primary bone-marrow mesenchymal cells. Knock down of DKK1 reduced dexamethasone-induced apoptosis of mesenchymal cells. Taken together, promoted DKK1 expression was associated with bone cell apoptosis in the occurrence of ONFH patients with the histories of corticosteroid and alcohol intake and progression of ONFH. DKK1 expression in injured tissue provides new insight into ONFH pathogenesis.
Ko
Jih-Yang
JY
Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Niao-Sung, Kaohsiung 833, Taiwan.
Wang
Feng-Sheng
FS
Wang
Ching-Jen
CJ
Wong
To
T
Chou
Wen-Yi
WY
Tseng
Shin-Ling
SL
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D005260:Female; D005271:Femur Head Necrosis / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
D051033:Apoptosis Inducing Factor; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins