Abstract
Osteonecrosis of femoral head (ONFH) is a progressive hip joint disease without disease-modifying treatment. Lacking understanding of the pathophysiological process of ONFH has become the humper to develop therapeutic approach. Serum amyloid A (SAA) is an acute phase lipophilic protein during inflammation and we found that SAA is increased for the first time in the serum of ONFH patients through proteomic studies and quantitatively verified by ELISA. Treating rBMSCs with SAA inhibited the osteogenic differentiation via Wnt/β-catenin signaling pathway deactivation and enhanced the adipogenic differentiation via MAPK/PPARγ signaling pathway activation. Finally, bilateral critical-sized calvarial-defect rat model which received SAA treated rBMSCs demonstrated reduction of bone formation when compared to untreated rBMSCs implantation control. Hence, SAA is a vital protein in the physiological process of ONFH and can act as a potential therapeutic target to treat ONFH.
Highlights
Osteonecrosis of femoral head (ONFH) is a progressive hip joint disorder without consensus of effective treatment, leading to total hip replacement (Mont et al, 2006)
Because adipocyte is found proliferated in ONFH, we further investigated whether Serum amyloid A (SAA) had other effects on the differentiation of rBMSCs
Tracing the history of ONFH, research of its pathogenesis has been ongoing since the disease was described by Jean Cruveilhier, a French anatomist and pathologist but keeps incompletely understood (Dubois and Cozen, 1960)
Summary
Osteonecrosis of femoral head (ONFH) is a progressive hip joint disorder without consensus of effective treatment, leading to total hip replacement (Mont et al, 2006). Overuse of alcohol and trauma of femoral neck or head are the three well known risk factors for ONFH. Previous study has indicated that the pathogenesis of ONFH is related to the severe degradation of the bone tissue (Weinstein et al, 2000), promoted differentiation of bone mesenchymal stem cells (BMSCs) to adipocytes and hypertrophy of the adipocyte through increasing intracellular lipid synthesis (Peckett et al, 2011). The increase of marrow fat cell induces intra-osseous hypertension in the proximal femur. Venous sinusoids are compressed due to the intra-osseous hypertension and intravascular coagulation occurs. Arterial blood flow is blocked and eventually results in ischemia in the femoral head (Yoon et al, 2020). The specific underlying molecular mechanism of aberrant bone metabolic balance has not been completely elucidated
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