OSTEOGENESIS AND ADIPOGENESIS OF THE BONE MARROW IN OSTEONECROSIS OF FEMORAL HEAD

Jae-Suk Chang, Ho-Saeng Moon, Mi-Jung Kim*, Jung-Hwa Kim*
Dept. of Orthop. Surg., Ulsan University, Seoul, KOREA
*Asan Institute for Life Sciences, Seoul, KOREA

The etiology of the osteonecrosis (ON) of the femoral head is not clear, but corticosteroids and alcohol abuse account for approximately 90% of all reported causes of ON, and corticosteroid or alcohol can change fat metabolism and induce hyperlipemia, which increase the fat content and size of the fat cells within the femoral head and increase the intracortical pressure. Hyperlipemia can also produce the fat embolism directed toward the femoral head, which occludes the microvasculature.

Frequently we've found hyperlipemia, especially triglyceride in ON. The bone marrow was also infiltrated with lipids, but it isn't clear whether the fat in the marrow was accumulated due to hyperlipemia or increased proliferation of the fat cell in bone marrow.

This study was aimed to identify the direction of the differentiation of the bone marrow cells toward osteogenesis or adipogenesis. And we've tried to analyze the proportion of the osteogenic presursor and the adipogenic precursors.

Bone marrow stromal cells have multipotency to differentiate into osteoblast, chondrocyte, adipocyte and fibroblast. And hormones, local factors and environments influence the direction of differentiation. Osteogenic cells and adipocyte share a precursor in common and there is some degree of plasticity and an inverse relationship between the osteogenic and adipocytic differentiation.

We designed the study to demonstrate the percentage of the STRO-1-positive cells for osteogenic potential using flow cytometry and the expression of PPARg2 for adipogenesis using reverse transcriptase polymerase chain reaction (RT-PCR) from the marrow cells obtained in the proximal femur of the patiens with femoral head ON.

For osteogenic cells, there is no well defined cell surface marker except STRO-1. Although all of STRO-1-positive cells are not destined to differentiate into the osteogenic cells and could differentiated into some other cells, the osteoprogenitors in human bone marrow are restricted to a subpopulation of TRO-1-positive cells.

Members of the PPAEs (peroxisome proliferator activated receptors superfamily) have been implicated in the control of the lipid matabolism and adipocyte differentiation PPARg2 is expressed in adipose tissue-specific manner and expression of PPARg2 is sufficient to convert fibroblastic or bone marrow stromal cells with little or no inherent adipogenic potential into preadipocytes. PPARg2 is a nuclear receptor of the heterodimeric structure with RXR (retinoic X receptor). As a transcriptional factor, the PPARg2 induces genes for the adipocyte-specific proteins that are involved in lipid metabolism, such as a P2 (adipocyte fatty acid binding protein), LPL (liproprotein lipase) and ACS (acyl-CoA synthetase), and induces adipocyte differentiation.

There were 4 groups of patients as follows:

The amount of fat was increased in the bone marrow of the osteonecrosis, but the origin was not certain; circulating fat from the liver or increased fat cell differentiation from the bone marrow cells. And this study was performed to identify whether the bone marrow cells of the osteonecrosis tend to differentiate into osteogenesis or adipogenesis.

We've obtained bone marrow cells from 21 cases of the osteonecrosis, 7 cases of osteoarthritis and 9 cases of femur neck fractures. For osteogenesis, the percentage of the STRO-1-positive cells, capable to differentiate into osteoblasts, were analyzed by the flow cytometry and it was lower in osteonecrosis than femoral neck fracture or osteoarthritis. PPARy2 is a transcription factor stimulating adipogenesis and its expression was identified by RT-PCR and its expression was positive in five of nine patients with osteonecrosis, but negative in the femoral neck fracture or osteoarthritis.

These findings showed that there was inverse relationship between the osteogenesis and adipogenesis in bone marrow of the proximal femur in osteonecrosis, and suggested that increased differentiation into fat cell of the marrow cell may cause fatty marrow in the osteonecrosis of the femoral head.