LRRC17 regulates the bone metabolism of human bone marrow mesenchymal stem cells from patients with idiopathic necrosis of femoral head through Wnt signaling pathways: A preliminary report.

Abstract

Idiopathic necrosis of the femoral head (INFH) is a common disease with unknown cause. Its successful treatment relies on the repair of the necrotic bone. The application of autologous mesenchymal stem cells (MSCs) has shown great promise in saving the patients from undergoing total hip arthroplasty. Leucine-rich repeat-containing 17 (LRRC17) is less expressed in patients with femoral head necrosis and LRRC17 can inhibit bone degradation. However, it remains unknown whether LRRC17 plays a role in the pathogenesis of INFH. The present study aimed to investigate the potential role and mechanism of LRRC17 in the pathogenesis and treatment of INFH. It was found that despite the similar cell morphology and MSC surface marker expressions of human bone marrow MSCs (BMSCs) isolated from patients with INFH (INFH-hBMSC) and femoral neck fracture (FNF) (FNF-hBMSC), INFH-hBMSC had higher percentage of apoptosis (P<0.05), as well as lower osteogenic potential and higher adipogenic potential (both P<0.05). However, there was no difference in cell proliferation between FNF-hBMSC and INFH-hBMSC (P>0.05). It was also confirmed that the expression of LRRC17 was lower in the bone tissue and hBMSCs from patients with INFH compared with patients with FNF (P<0.05). Overexpression of LRRC17 promoted osteogenesis and inhibited the adipogenesis in hBMSCs, accompanied with the increase of Wnt3a and β-catenin expressions, and the decrease of Wnt5a and receptor activator of nuclear factor κ-B ligand (Rankl) expressions (all, P<0.05). Furthermore, knockout of LRRC17 in hBMSCs inhibited the expression levels of osteogenic and promoted adipogenic markers, while decreasing Wnt3a and β-catenin expressions, and increasing Wnt5a and Rankl expressions (all, P<0.05). The present preliminary study suggested that imbalanced bone metabolism may be involved in the pathogenesis of INFH. The modulation of the LRRC17 gene may delay or even restore the balance of osteogenic and adipogenic differentiation in autologous BMSCs derived from patients with INFH, providing a new target for the treatment of INFH.