Kuei-Lu-Er-Xian-Jiao extract enhances BMP-2 production in osteoblasts

Osteoporosis is a common skeletal disorder, resulting from an imbalance in bone resorption relative to formation. Bone morphogenetic protein (BMP) is a key regulator in bone formation and osteoblastic differentiation. Hence, compounds that promote BMP expression may be suitable candidates for osteoporosis treatment. This study examined the effects of the traditional Chinese medicinal agent, Kuei-Lu-Er-Xian-Jiao (KLEXJ), on BMP-2 production in osteoblasts. We found that KLEXJ extract promoted osteoblastic differentiation marker ALP activity and increased BMP-2 production; pretreatment with PI3K and Akt inhibitors, or small interfering RNA (siRNA), reduced these effects. KLEXJ also enhanced PI3K and Akt phosphorylation. Treatment of osteoblastic cells with NF-κB inhibitors (TPCK or PDTC) markedly inhibited KLEXJ-enhancement of ALP activity and BMP-2 production. KLEXJ also significantly promoted p65 phosphorylation, while treatment with PI3K and Akt inhibitors antagonized KLEXJ-enhanced p65 phosphorylation. Thus, KLEXJ enhances ALP activity and BMP-2 production of osteoblasts through the PI3K/Akt/ NF-κB signaling pathway and hence may be suitable in the treatment of osteoporosis.