Effects of tanshinol on markers of bone turnover in ovariectomized rats and osteoblast cultures
July
Effects of tanshinol on markers of bone turnover in ovariectomized rats and osteoblast cultures
Jianfeng Han 1 2
Wei Wang 0 2
0 Department of Endocrinology, The 2nd Affiliated Hospital of Harbin Medical University , Harbin , China
1 Department of Orthopedics, The 2nd Affiliated Hospital of Harbin Medical University , Harbin , China
2 Editor: Andre van Wijnen, University of Massachusetts Medical School , UNITED STATES
This study was aimed to explore the role of tanshinol in osteoblastic cells, and the role in vivo using an ovariectomized (OVX) rat model of osteoporosis. MC3T3-E1 cells were pretreated with 0±400 μg/mL tanshinol, and then cell viability, apoptosis, alkaline phosphatase (ALP) activity and the expressions of Collagen Type I Alpha 1 (Col1A1), Runt Related Transcription Factor 2 (Runx2) and osteocalcin (OCN) were respectively detected. Rats underwent OVX surgery was intervened with 5 mg/kg tanshinol or 25 μg/kg β-estradiol (E2) for 12 weeks. The triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C), ALP, OCN and Tartrate-resistant acid phosphatase-5b (TRACP-5b) contents were measured. Besides, the expressions of main factors in nuclear factor-kappa B (NF-κB) pathway were detected. The results showed that tanshinol significantly promoted MC3T3-E1 cells viability and ALP activity, while inhibited apoptosis (P < 0.05); Col1A1, Runx2 and OCN were all up-regulated by tanshinol (P < 0.05). In OVX rats, the contents of TG, TC, LDL-C, ALP, OCN and TRACP-5b were all increased (P < 0.05), while HDL-C was decreased (P < 0.05). Tanshinol significantly alleviated these aberrant regulations (P < 0.05). Inhibitory subunit of NF-κB (IκBα) and p65 were both remarkably phosphorylated by OVX, while this phosphorylation was partially neutralized by tanshinol (P < 0.05). In conclusion, we demonstrated that tanshinol exerted a bone-protective function by modulating the markers of bone turnover possibly via blocking NF-κB pathway. This study will provide new evidence that tanshinol is a potential therapeutic option for the relief of estrogen deficiency-induced osteoporosis.
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Data Availability Statement: All relevant data are
within the paper.
Funding: The authors received no specific funding
for this work.
Competing interests: The authors have declared
that no competing interests exist.
Introduction
Osteoporosis is one type of bone metabolic disease characterized by low bone mineral density
and deterioration of the bone microarchitecture [
1
]. It is an increasingly important health
problem which affects millions of people worldwide with significant impact on morbidity,
mortality, quality of life and cost [
2
]. The most important risk factors of osteoporosis are
advanced age and female sex, and estrogen deficiency following menopause or ovariectomized
(OVX) surgery is correlated with a rapid reduction in bone mineral density [
3
]. In the bone,
osteoblasts are responsible for bone formation while the duty of osteoclasts is bone resorption,
that is, bone growth is maintained by the coordination of osteoblasts and osteoclasts [
4
].
Osteoblast differentiation, an important process for its function, confers marked rigidity and
strength to the bone while still maintaining some degree of elasticity [
5
]. Thus, it is beneficial
for osteoporosis prevention and treatment to investigate how to promote osteoblast
differentiation and increase bone mass.
Tanshinol, 3-(3,4-Dihydroxyphenyl)-2-hydroxypropanoic acid, also known as danshensu is
a water-soluble components of Salvia miltiorrhiza Bunge [
6
]. Tanshinol is a polyphenolic
compound with two phenolic hydroxyl groups, and because of this it has been identified as an
effective natural product antioxidant [
7
]. In China, it is widely used in traditional medicine for
myocardial infarction, coronary heart disease, atherosclerosis, hypertension, hyperlipoidemia,
thrombopoiesis and acute ischemic stroke. In terms of osteoporosis, previous studies have
indicated tanshinol stimulated bone formation and attenuated dexamethasone-induced
inhibition of osteogenesis in larval zebrafish [
6
]. Additionally, in vitro investigation has provided
evidences that tanshinol could antagonize glucocorticoids-induced osteoporosis by controlling
osteoblast apoptosis [
8
]. However, the influence of tanshinol on osteoblastic differentiation
and OVX-induced osteoporosis has not been exhaustively investigated.
In the present study, mouse osteoblastic cell line MC3T3-E1 was used and pretreated with
tanshinol, to explore the role of tanshinol in osteoblastic cells. Moreover, female rats
underwent OVX surgery and tanshinol intervention were used to test whether tanshinol has
functional effects on OVX-induced dyslipidemia and bone turnover in vivo. Furthermore, the
main factors in nuclear factor-kappa B (NF-κB) pathway were detected to obtain a possible
understanding of tanshinol in OVX-induced osteoporosis deepen into (...truncated)