Mitochondrial quality control and its role in osteoporosis

Abstract

Mitochondria are important organelles that provide cellular energy and play a vital role in cell differentiation and apoptosis. Osteoporosis is a chronic metabolic bone disease mainly caused by an imbalance in osteoblast and osteoclast activity. Under physiological conditions, mitochondria regulate the balance between osteogenesis and osteoclast activity and maintain bone homeostasis. Under pathological conditions, mitochondrial dysfunction alters this balance; this disruption is important in the pathogenesis of osteoporosis. Because of the role of mitochondrial dysfunction in osteoporosis, mitochondrial function can be targeted therapeutically in osteoporosis-related diseases. This article reviews different aspects of the pathological mechanism of mitochondrial dysfunction in osteoporosis, including mitochondrial fusion and fission, mitochondrial biogenesis, and mitophagy, and highlights targeted therapy of mitochondria in osteoporosis (diabetes induced osteoporosis and postmenopausal osteoporosis) to provide novel targets and prevention strategies for the prevention and treatment of osteoporosis and other chronic bone diseases.

Keywords: mitochondrial autophagy; mitochondrial biogenesis; mitochondrial fusion and fission; osteoporosis; targeted therapy.

Figure 1

Mitochondrial dynamics are involved in the mechanisms of the regulation of osteoporosis. Mechanisms of mitochondrial dynamics (mitochondrial fusion and fission) that regulate osteoblasts and osteoclasts in osteoporosis. The arrows indicate activation and the inhibitory arrows indicate inhibition.

Figure 2

Mitochondrial biogenesis is involved in the mechanisms of regulation of osteoporosis. Mechanisms of mitochondrial biogenesis that regulate osteoblasts and osteoclasts in osteoporosis. The arrows indicate activation and the inhibitory arrows indicate inhibition.

Figure 3

Mitophagy is involved in the mechanisms of the regulation of osteoporosis. Mechanisms of mitophagy regulate osteoblasts and osteoclasts in osteoporosis. The arrows indicate activation and the inhibitory arrows indicate inhibition.

Figure 4

The mechanism and potential targeted therapy of mitochondria in osteoporosis. Mechanisms of mitochondrial dysfunction regulating osteoblasts and osteoclasts in osteoporosis; Mitochondrial dysfunction may have potential relationship with ferroptosis, and traditional Chinese medicine and natural medicine targeting mitochondria may have therapeutic effects.

Figure 5

Mitochondrial dysfunction is involved in the mechanism of osteoporosis. Mitochondrial dysfunction (mitochondrial dynamics, mitochondrial biogenesis, and mitophagy) leading to the development and progression of osteoporosis. The main targets of mitochondrial dysfunction are DRP1, OPA1, GSK-3β, mTOR, SIRT1/3, PGC-1α, NRF2/2, PINK1, and Parkin.