Biglycan， a small leucine rich proteoglycan (SLRP)， is an important participant in bone homeostasis and development as well as in bone pathology. In the present study biglycan was identified as a positive regulator of MG63 osteosarcoma cell growth ( ≤ 0.001). IGF-I was shown to increase biglycan expression ( ≤ 0.01)， whereas biglycan-deficiency attenuated significantly both basal and IGF-I induced cell proliferation of MG63 cells ≤ 0.001; ≤ 0.01， respectively). These effects were executed through the IGF-IR receptor whose activation was strongly attenuated ( ≤ 0.01) in biglycan-deficient MG63 cells. Biglycan， previously shown to regulate Wnt/β-catenin pathway， was demonstrated to induce... More
Biglycan， a small leucine rich proteoglycan (SLRP)， is an important participant in bone homeostasis and development as well as in bone pathology. In the present study biglycan was identified as a positive regulator of MG63 osteosarcoma cell growth ( ≤ 0.001). IGF-I was shown to increase biglycan expression ( ≤ 0.01)， whereas biglycan-deficiency attenuated significantly both basal and IGF-I induced cell proliferation of MG63 cells ≤ 0.001; ≤ 0.01， respectively). These effects were executed through the IGF-IR receptor whose activation was strongly attenuated ( ≤ 0.01) in biglycan-deficient MG63 cells. Biglycan， previously shown to regulate Wnt/β-catenin pathway， was demonstrated to induce a significant increase in β-catenin protein expression evident at cytoplasmic ( ≤ 0.01)， membrane ( ≤ 0.01)， and nucleus fractions in MG63 cells ( ≤ 0.05). As demonstrated by immunofluorescence， increase in β-catenin expression is attributed to co-localization of biglycan with the Wnt co-receptor low-density lipoprotein receptor-related protein 6 (LRP6) resulting in attenuated β-catenin degradation. Furthermore， applying anti-β-catenin and anti-pIGF-IR antibodies to MG-63 cells demonstrated a cytoplasmic and to the membrane interaction between these molecules that increased upon exogenous biglycan treatment. In parallel， the downregulation of biglycan significantly inhibited both basal and IGF-I-dependent ERK1/2 activation， ( ≤ 0.001). In summary， we report a novel mechanism where biglycan through a LRP6/β-catenin/IGF-IR signaling axis enhances osteosarcoma cell growth.
