Taurine Inhibits Glucocorticoid-Induced Bone Mitochondrial Injury, Preventing Osteonecrosis in Rabbits and Cultured Osteocytes

Abstract

Mitochondrial injury has recently been implicated in the pathogenesis of glucocorticoid-induced osteonecrosis. Using cultured osteocytes and a rabbit model, we investigated the possibility that taurine (TAU), which is known to play a role in the preservation of mitochondrial function, might also prevent the development of osteonecrosis. To reduplicate the intraosseous environment seen in glucocorticoid-induced osteonecrosis, dexamethasone (Dex) was added to MLO-Y4 cultured in 1% hypoxia (H-D stress environment). An in vitro study was conducted in which changes in mitochondrial transcription factor A (TFAM), a marker of mitochondrial function, and ATP5A produced by mitochondria, induced by the presence/absence of taurine addition were measured. To confirm the effect of taurine in vivo, 15 Japanese White rabbits were administered methylprednisolone (MP) 20 mg/kg as a single injection into the gluteus muscle (MP+/TAU− group), while for 5 consecutive days from the day of MP administration, taurine 100 mg/kg was administered to 15 animals (MP+/TAU+ group). As a control 15 untreated rabbits were also studied. The rabbits in each of the groups were sacrificed on the 14th day after glucocorticoid administration, and the bilateral femora were harvested. Histopathologically, the incidence of osteonecrosis was quantified immunohistochemically by quantifying TFAM and ATP5A expression. In the rabbits exposed to an H-D stress environment and in MP+/TAU− group, TFAM and ATP5A expression markedly decreased. With addition of taurine in the in vitro and in vivo studies, the expression of TFAM and ATP5A was somewhat decreased as compared with Dex−/hypoxia− or MP−/TAU− group, while improvement was noted as compared with Dex+/hypoxia+ or MP+/TAU− group. In rabbits, the incidence of osteonecrosis was 80% in MP+/TAU− group, in contrast to 20% in the taurine administered group (MP+/TAU+), representing a significant decrease. Since taurine was documented to exert a protective effect on mitochondrial function by inhibiting the mitochondrial dysfunction associated with glucocorticoid administration, we speculated that it might also indirectly help to prevent the development of osteonecrosis in this context. Since taurine is already being used clinically, we considered that its clinical application would also likely be smooth.

Long-Term Dietary Taurine Lowers Plasma Levels of Cholesterol and Bile Acids

“…To be exact, 7-oxocholesterol is a substrate of 11B-HSD1 [67,68]. Taurine reportedly prevents glucocorticoid-induced osteonecrosis and muscle atrophy, which implies that taurine may affect the activity of 11B-HSD1 and suppress glucocorticoid-induced physiological reactions [69,70]. Despite no direct evidence of the relationship between taurine and 11B-HSD, taurine may contribute to cholesterol metabolism via not only increased expression of Cyp7a1, but also regulation of the activity of 11B-HSD1.…”

Taurine as a Natural Antioxidant: From Direct Antioxidant Effects to Protective Action in Various Toxicological Models

“…Importantly, oxidised proteins and amino acids can cause oxidative stress [ 146 ]. Furthermore, in rabbits and cultured osteocytes, Tau was shown to inhibit glucocorticoid-induced bone mitochondrial injury and to mitigate osteonecrosis [ 147 ]. Pre-treatment of mouse testicular mitochondria, exposed to bisphenol A, with 30 and 50 µmol/L of Tau was reported to suppress mitochondrial oxidative stress and to restore mitochondrial membrane potential [ 148 ].…”

Glucocorticoid-Induced Osteocytic Cell Death in a Hypoxic Environment Is Associated with Necroptosis

“…MLO-Y4 cells seeded in type I collagen-coated 4-chamber culture slides (BD Biosciences, Bedford, MA, USA) were cultured overnight. A total of 1 µM Dex (MSD, Tokyo, Japan) was added to MLO-Y4 in a hypoxia environment (H-D stress environment) [3], and then, after the addition of 50 µM necrostatitin-1 (Nec-1, abcam, Cambridge, UK), cultured for 24 h (Dex(+)/hypoxia(+)/Nec-1 group). In addition, MLO-Y4 was cultured for 12 h in an H-D stress environment, followed by the addition of Nec-1.…”

“…Although numerous studies have focused on issues, such as the underlying pathophysiology and prevention of glucocorticoid-associated femoral head osteonecrosis, its causes and preventative strategies remain to be established. Glucocorticoid-associated femoral head osteonecrosis has been generally attributed to an ischemic-hypoxia event, but more recently factors such as oxidative injury and mitochondrial injury have also been implicated [1][2][3].…”