Abstract
Naringin maintains bone mass in various osteoporosis models, while its effect on bone in disuse osteoporosis has not been reported. The present study explores whether naringin can prevent disuse osteoporosis induced by unilateral sciatic neurectomy (USN) and whether the Semaphorin 3A-induced Wnt/β-catenin signalling pathway is involved in the osteoprotection of naringin. Naringin dose-dependently prevented the deterioration of bone mineral density (BMD), trabecular structure and biomechanical strength in femur due to USN. Naringin increased bone formation but inhibited resorption, as indicated by bone-turnover markers in blood and urine and the histological staining of Osteocalcin (OCN) and tartrate-resistant acid phosphatase (TRAP) in femur. Semaphorin 3A (Sema3A) and active β-catenin protein decreased after USN and could be restored by naringin to the levels of the sham-operated rats. In addition, naringin in vitro promoted the differentiation of osteoblasts and inhibited osteoclastic differentiation. Our studies suggest that the down-regulation of Sema3A and the subsequent inactivation of Wnt/β-catenin signalling may be some of the mechanisms involved in USN-induced osteoporosis. Naringin could increase the expression of Sema3A and the activation of Wnt/β-catenin signalling to prevent disuse osteoporosis induced by denervation. Thus, naringin functions in bone maintenance and could be a promising therapeutic alternative in preventing disuse osteoporosis.
Highlights
Semaphorin 3A (Sema3A), a secreted soluble protein, was originally identified as an axonal guidance chemorepellent with an essential role in nerve system (NS) development[1] and regeneration following injury[2]; it belongs to the Semaphorin protein family[3]
Because the sciatic nerve provides nerve fibres innervating the cancellous bone of the femur and tibia[15] and because Sema3A derived from peripheral neurons and generated locally by osteoblasts and osteocytes plays a beneficial role in bone mass protection, we use here the transecting unilateral sciatic nerve model to investigate whether a change in the Sema3A signal is involved in bone loss induced by unilateral sciatic neurectomy (USN), which induces disused osteoporosis and is widely used in studies focusing on immobilization osteoporosis[12,28], and whether naringin can prevent USN-induced osteoporosis and its corresponding mechanism
Naringin has been extensively studied for its protective role in the maintenance of bone mass in various models of osteoporosis; no report has investigated the effect of naringin on disuse osteoporosis or its corresponding mechanism
Summary
Semaphorin 3A (Sema3A), a secreted soluble protein, was originally identified as an axonal guidance chemorepellent with an essential role in nerve system (NS) development[1] and regeneration following injury[2]; it belongs to the Semaphorin protein family[3]. Because nerves innervating bone and neuropeptides within the bone microenvironment play an important role in the regulation of bone homeostasis[16,17], it is hypothesized that, in addition to immobilization, the disturbance of peripheral neuron-derived signals contributes to osteopenia induced by peripheral nerve neurectomy. Because the sciatic nerve provides nerve fibres innervating the cancellous bone of the femur and tibia[15] and because Sema3A derived from peripheral neurons and generated locally by osteoblasts and osteocytes plays a beneficial role in bone mass protection, we use here the transecting unilateral sciatic nerve model to investigate whether a change in the Sema3A signal is involved in bone loss induced by unilateral sciatic neurectomy (USN), which induces disused osteoporosis and is widely used in studies focusing on immobilization osteoporosis[12,28], and whether naringin can prevent USN-induced osteoporosis and its corresponding mechanism
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