Serum Insufficiency Induces RANKL-Independent Osteoclast Formation during Developing Ischemic ONFH.

Yi-min Hsiao,Yu-Tien Chiu,Yuhan Chang,Mei-Feng Chen,Chih-Hsiang Chang,Chih-Chien Hu

doi:10.3390/biomedicines9060685

Yi-min Hsiao, Yu-Tien Chiu + Show 4 more

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https://doi.org/10.3390/biomedicines9060685

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Journal: Biomedicines	Publication Date: Jun 17, 2021
Citations: 7	License type: CC BY 4.0

Affiliation: Chang Gung Memorial Hospital, Chang Gung University

Abstract

Blood supply interruption induces hypoxia and reduces serum provision to cause ischemia-induced osteonecrosis, including avascular osteonecrosis of the femoral head (ONFH). Oxygen deficiency (hypoxia) is known to induce different expression patterns in osteoblasts and osteoclasts, which have been extensively studied. However, the effects of serum insufficiency in nutrients, growth factors, and hormones on osteoblast and osteoclast activity in the damaged area and nearby regions remain poorly understood. In this study, the expression of osteoblast and osteoclast marker proteins was elucidated through in vitro and ex vivo studies. The results indicate that serum insufficiency accelerates the formation of monocyte-derived osteoclasts. The combined effect of serum insufficiency and hypoxia (mimicking ischemia) suppressed the activity of alkaline phosphatase and calcification in osteoblasts after the stimulation of osteogenic growth factors. Serum insufficiency increased the activity of tartrate-resistant acid phosphatase, expression of phosphorylated extracellular signal-regulated kinases, and production of reactive oxygen species in monocyte-derived osteoclasts in the absence of receptor activator of nuclear factor kappa-Β ligand stimulation. The findings indicate that changes in the expression of osteoblast and osteoclast markers in necrotic bone extracts were similar to those observed during an in vitro study. These results also suggest that serum insufficiency may be involved in the regulation of osteoclast formation in patients with ONFH.

Highlights

This study combined the results of in vitro culturing of osteoblast and osteoclast precursors to elucidate the effects of serum insufficiency alone and in combination with ischemia in disrupting the balance of osteoblast and osteoclast formation, as observed in patients with ONFH
Serum insufficiency increased the formation of monocyte-derived osteoclasts in vitro, regardless of whether serum insufficiency occurred in combination with hypoxia
The decrease in cell density observed under conditions of serum insufficiency and ischemia may be attributable to the acceleration of preosteoclast fusion (Figure 1) or the possible inhibition of osteoclast formation after serum reperfusion reduced the number of osteoclasts (Figure 3)

Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Osteonecrosis of the femoral head (ONFH) is a pathological condition of the hip joint that is caused by disruption of the blood supply to the femoral head [1,2]. Symptoms of soft tissue necrosis, including cell swelling and inflammatory responses, do not occur in ONFH, and the exact mechanism of this ischemic disease is unknown [3,4]. The interruption in blood supply that is a pathophysiological characteristic of this disease induces ischemia (serum (nutrient) insufficiency and hypoxia), which disrupts the balance of osteoblast and osteoclast activity at the damaged area of the femoral head during ONFH progression [5,6,7]

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