Autophagy: An important target for natural products in the treatment of bone metabolic diseases

Abstract

Bone homeostasis depends on a precise dynamic balance between bone resorption and bone formation, involving a series of complex and highly regulated steps. Any imbalance in this process can cause disturbances in bone metabolism and lead to the development of many associated bone diseases. Autophagy, one of the fundamental pathways for the degradation and recycling of proteins and organelles, is a fundamental process that regulates cellular and organismal homeostasis. Importantly, basic levels of autophagy are present in all types of bone-associated cells. Due to the cyclic nature of autophagy and the ongoing bone metabolism processes, autophagy is considered a new participant in bone maintenance. Novel therapeutic targets have emerged as a result of new mechanisms, and bone metabolism can be controlled by interfering with autophagy by focusing on certain regulatory molecules in autophagy. In parallel, several studies have reported that various natural products exhibit a good potential to mediate autophagy for the treatment of metabolic bone diseases. Therefore, we briefly described the process of autophagy, emphasizing its function in different cell types involved in bone development and metabolism (including bone marrow mesenchymal stem cells, osteoblasts, osteocytes, chondrocytes, and osteoclasts), and also summarized research advances in natural product-mediated autophagy for the treatment of metabolic bone disease caused by dysfunction of these cells (including osteoporosis, rheumatoid joints, osteoarthritis, fracture nonunion/delayed union). The objective of the study was to identify the function that autophagy serves in metabolic bone disease and the effects, potential, and challenges of natural products for the treatment of these diseases by targeting autophagy.

Machine learning identifies ferroptosis-related genes as potential diagnostic biomarkers for osteoarthritis

“…found that the PI3K and Akt content decreased in OA ( 18 ), which may lead to a reduction in the PI3K/Akt pathway activity. Then reduces the activity of its downstream target mTOR, a key autophagy inhibitor, resulting in abnormal activation of cellular autophagy in OA and synergistic activation of massive chondrocyte apoptosis in the joint ( 19 ). At the same time, mitochondrial autophagy, a form of selective autophagy, engulfs large amounts of ferritin, leading to excessive Fe 2+ release, increasing the intracellular pool of unstable iron and thus leading to chondrocyte ferroptosis ( 4 ).…”

Epigenetic Regulation of Autophagy in Bone Metabolism

“…The process of autophagy encompasses not only the osteoclastic resorption process but also the acquisition of energy sources during osteoblast differentiation. 140 Altered autophagy can disrupt bone cell balance, potentially causing various diseases.…”

“…Furthermore, given the unique features of terminal differentiation, the prolonged lifespan of bone cells, and their oxygen and nutrient-deprived environment, autophagy becomes a key player in the regular physiological processes of these cells. 140 , 163 Unsurprisingly, osteocytes exhibit a notable baseline level of autophagy both in laboratory settings and within living organisms. Selectively deleting the autophagy-related gene ATG7 in osteocytes inhibits autophagy, causing decreased bone formation and reduced bone mass in young adult mice, resembling the effects of aging on the skeletal system.…”