Abstract
Periostin is a matricellular protein, which seems to play an important role as an anabolic factor in bone tissue development and repair. By binding to cell surface receptors, it can modulate cell adhesion, proliferation, and differentiation, as well as cell-matrix interaction. Periostin is involved in collagen folding, a process which is crucial for matrix assembly and, therefore, for bone strength. However, its exact function on bone biology has not been fully clarified. Patients with hemoglobinopathies develop frequently bone loss, leading to osteopenia or osteoporosis. Several factors are implicated in the pathogenesis of bone destruction in these disorders. Our group has recently shown that activin-A is another factor which contributes to low bone mineral density (BMD) in thalassemia major (TM). Intriguingly, current studies have reported that periostin expression is up-regulated by several members of the TGF-β superfamily, including activin-A. Therefore, the aim of this study was to evaluate circulating periostin levels in a large number of patients with hemoglobinopathies and explore possible correlations with clinical and laboratory data, including BMD and circulating activin-A levels.
We studied prospectively 162 patients with hemoglobinopathies: 47 patients had beta-thalassemia major (TM), 30 beta-thalassemia intermedia (TI), 75 double heterozygous sickle-cell/beta-thalassemia (HbS/beta-thal) and 10 had homozygous sickle cell disease (SCD). Circulating periostin was measured in the serum of the patients using an enzyme immunoassay (USCN Life Science Inc, Wuhan, Hubei, China), which has an intra-assay CV<10% and an inter-assay CV<12%. Circulating activin-A was measured using also an enzyme immunoassay (R&D Systems, Minneapolis, MN, USA). BMD of the lumbar spine (L1-L4), femoral neck (FN) and distal radius (R) was measured by dual energy X-ray absorptiometry (DXA) in all patients, at the time of blood sampling, using the Norland XR-26 Mark II densitometer (Norland Scientific Instruments, Fort Atkinson, WI, USA). The in vitro precision by repeated daily phantom measurements was 0.7 %, while the in vivo precision was 1.4 %, established in the laboratory used, by double measurements at weekly intervals. The above molecules were also measured in the serum of 17, age- and gender-matched, healthy individuals who served as controls.
Patients with TM (mean±SD: 3227±1148 ng/ml), TI (2907±1255 ng/ml), HbS/beta-thal (3173±1244 ng/ml) and SCD (4300±1411 ng/ml) had elevated circulating periostin compared to controls (597±177 ng/ml, p<0.001 for all comparisons). Furthermore, SCD patients had higher periostin levels compared to patients with TI (p=0.005), HbS/beta-thal (p=0.026) and TM (p=0.029). In all patients, circulating periostin correlated weakly with activin-A (r=0.161, p=0.04), while in patients with HbS/beta-thal, high circulating periostin showed weak correlation with LDH (r=0.262, p=0.023). Regarding BMD, osteoporosis (according to the WHO definition based on DXA data) was present in 45% of patients with TM, in 40% of patients with TI, in 33% of SCD patients and in 25% of patients with HbS/beta-thal. Interestingly, high periostin levels strongly correlated with high BMD T-score of L1-L4 in HbS/beta-thal patients (r=0.740, p=0.006), but there were no other correlations between circulating periostin with BMD in the other subtypes of hemoglobinopathies.
Our data, the first in the literature on circulating periostin levels in patients with hemoglobinopathies, show that periostin is elevated in the serum of patients with all studied subtypes of hemoglobinopathies, but it correlates with high BMD only in patients with HbS/beta-thal. One possible explanation is that periostin correlates with bone repair and possibly patients with HbS/beta-thal have higher repair activity and thus lower bone loss, increased bone strength and lower incidence of osteoporosis compared to other hemoglobinopathies patients. Furthermore, the presence of different periostin isoforms with unknown activity on bone remodeling may also explain these differences. Further studies are necessary to understand the regulation of periostin and its biological activities in the bone of patients with hemoglobinopathies.
Disclosures:
No relevant conflicts of interest to declare.
ANTIOSTEOPOROTIC ACTIVITY OF ANTHRAQUINONE ISOLATED FROM MORINDA CITRIFOLIA FRUITS IN RATS
