Abstract

Objective Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation potential, which allows them to progress to osteogenesis, adipogenesis, and chondrogenesis. An imbalance of differentiation between osteogenesis and adipogenesis will result in pathologic conditions inside the bone. This type of imbalance is also one of the pathological findings in osteonecrosis of the femoral head (ONFH). Chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was previously reported to mediate the differentiation of mesenchymal stem cells. This study investigated the expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, and COUP-TFII in the femoral head tissue harvested from ONFH patients, and characterized the effect of COUP-TFII on the differentiation of primary BMSCs. MethodsThirty patients with ONFH were recruited and separated into 3 groups: the trauma-, steroid- and alcohol-induced ONFH groups (10 patients each). Bone specimens were harvested from patients who underwent hip arthroplasty, and another 10 specimens were harvested from femoral neck fracture patients as the control group. Expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, C/EBP-α, and COUP-TFII was analyzed by Western blotting. Primary bone marrow mesenchymal cells were harvested from ONFH cells treated with COUP-TFII RNA interference to evaluate the effect of COUP-TFII on MSCs. ResultsONFH patients had significantly increased expression of the adipogenesis regulator PPARγ and C/EBP-α and decreased expression of the osteogenesis regulator osteocalcin. ONFH bone tissue also revealed higher COUP-TFII expression. Immunohistochemical staining displayed strong COUP-TFII immunoreactivity adjacent to osteonecrotic trabecular bone. Increased COUP-TFII expression in the bone tissue correlated with increased PPARγ and decreased osteocalcin expression. Knockdown of COUP-TFII with siRNA in BMSCs reduced adipogenesis and increased osteogenesis in mesenchymal cells. ConclusionIncreased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. This study might reveal a new target in the treatment of ONFH.

Highlights

  • Femoral head osteonecrosis, known as avascular necrosis, was previously considered a pathological state that causes decreased vascular supply to the subchondral bone of the femoral head, resulting in osteocyte death and collapse of the articular surface

  • Recent data suggest that ONFH is a multisystemic disease rather than a simple disease of the femoral head [1,2,3,4,5,6]. ere are indications that osteonecrosis can be induced by decreased blood supply, increased marrow pressure, abnormal coagulation, or toxic effects on bone cells

  • To clarify the role of COUP-TFII in ONFH, we investigated the expression of the osteogenesis regulator Runx2, osteocalcin, the adipogenesis regulator PPARγ, and COUPTFII in the femoral head tissue harvested from ONFH patients and evaluated correlations among these factors. en, we further explored the effect of COUP-TFII on the differentiation of primary bone marrow mesenchymal stem cells (BMSCs)

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Summary

Objective

Bone marrow-derived mesenchymal stem cells (BMSCs) have multilineage differentiation potential, which allows them to progress to osteogenesis, adipogenesis, and chondrogenesis. Is study investigated the expression of the osteogenesis regulator Runx, osteocalcin, the adipogenesis regulator PPARγ, and COUP-TFII in the femoral head tissue harvested from ONFH patients, and characterized the effect of COUP-TFII on the differentiation of primary BMSCs. Methods. Expression of the osteogenesis regulator Runx, osteocalcin, the adipogenesis regulator PPARγ, C/EBP-α, and COUP-TFII was analyzed by Western blotting. ONFH patients had significantly increased expression of the adipogenesis regulator PPARγ and C/EBP-α and decreased expression of the osteogenesis regulator osteocalcin. Knockdown of COUP-TFII with siRNA in BMSCs reduced adipogenesis and increased osteogenesis in mesenchymal cells. Increased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. Increased COUP-TFII expression mediates the imbalance of BMSC differentiation and progression to ONFH in patients. is study might reveal a new target in the treatment of ONFH

Introduction
Materials and Methods
Osteogenic and Adipogenic Differentiation of Human
Results
Increased COUP-TFII Expression in the ONFH
Full Text
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