Role of autocrine osteopontin in promoting multiple functions of murine Nf1+/-osteoclast / 中华骨科杂志

ABSTRACT

Objective To detect the osteopontin (OPN) autocrine function of the osteoclasts in neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nfl+/+) mice.Test the osteoclasts function of neurofibromatosis type 1 heterozygote (Nfl+/-) and wild type (Nil+/+) mice with exogenous neutralizing OPN antibody,analysis the role of autocrine OPN in the hyperfunction of osteoclast in neurofibromatosis type 1.Methods Culture the low density bone marrow cells from Nfl heterozygote (Nfl+/-) and wild type (Nfl+/+) mice (4-6 weeks old) with macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand(RANKL),Measure.the OPN concentration in osteoclast culture superenant with ELISA.Culture the low density bone marrow cells from Nf1+/-and Nf1+/+ mice with or without exogenous neutralizing antibody for OPN.The function of osteoclasts and osteoclast progenitors in formation,migration,adhesion,and bone absorption were tested.Results A significantly higher concentration of OPN was detected in the Nf1+/-osteoclast culture media as compared to that of wild type.In control,Osteoclast functions,including migration,adhesion,and bone resorption of Nf1 +/-were higher than that of wild type.Addition OPN neutralizing antibody to the Nf1+/-OCL significantly reduced OCL formation.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL adhensiontion,Anti-OPN minimized OCL migration in both wild type and Nf1 +/-OCL cultures as measured by the transwell assays.Neutralizing OPN antibody diminished both wild type and Nf1+/-OCL pit formation,P＞0.05 for comparing Nfl+/-vs.wild type OCLs with anti-OPN antibody.Conclusion The hyperfunction of osteoclast in Nf1 heterozygote is related with autocrine osteopontin,inhibition of OPN may be an effective treatment for bone destruction of neurofibromatosis type 1.