Abstract
Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 μg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.
Highlights
Osteonecrosis of the femoral head (ONFH), a progressive bone disorder, causes subchondral bone microfractures and significant pain [1]. e age of patients ranged from 20 to 40 years [2]
To evaluate the influence of Tanshinone I (TsI) on the rat model of steroid-induced ONFH (SIONFH), SIONFH was induced by intraperitoneal injection of LPS and intramuscular injection of MPS according to a previous study [25], followed by intraperitoneal injection of low-dose or high-dose TsI
TsI treatment attenuated the MPS-induced osteonecrosis in the femoral heads (Figure 1(a)). e microarchitectural parameters including Bone mineral density (BMD), bone volume/total volume (BV/TV) ratio, Tb.N, Tb.Sp, and Tb. were quantified (Figures 1(b)– 1(f )). e values of these parameters in the SIONFH group (BMD, 0.19 ± 0.04 g/cm3; BV/TV ratio, 30.66% ± 4.17%; Tb.N, 2.07 ± 0.21/mm; Tb.Sp, 0.17 ± 0.01 mm; and Tb. , 0.08 ± 0.01 mm) were significantly lower than those in the control group (BMD, 0.34 ± 0.04 g/cm3; BV/TV ratio, 60.45% ± 3.57%; Tb.N, 5.71 ± 0.50/mm; Tb.Sp, 0.10 ± 0.01 mm; and Tb. , 0.14 ± 0.02 mm)
Summary
Osteonecrosis of the femoral head (ONFH), a progressive bone disorder, causes subchondral bone microfractures and significant pain [1]. e age of patients ranged from 20 to 40 years [2]. Osteonecrosis of the femoral head (ONFH), a progressive bone disorder, causes subchondral bone microfractures and significant pain [1]. E age of patients ranged from 20 to 40 years [2]. 80% of patients receiving surgery during the early stages suffer from femoral heads collapse within 1–3 years [3]. E femoral heads collapse may rapidly progress to hip osteoarthritis that severely impacts hip joint function, undergoing artificial joint replacement [3]. Patients with ONFH will suffer lifelong disability, which seriously affects the patients’ quality of life. ONFH can be categorized as traumatic and nontraumatic. As nontraumatic ONFH, steroid-induced ONFH (SIONFH) was diagnosed in 26.84% of the ONFH patients in China, behind alcohol-induced ONFH [4].
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