Abstract

Osteoporosis is a systemic bone disease characterized by reduced bone mass and deterioration of the microstructure of bone tissue, leading to an increased risk of fragility fractures and affecting human health worldwide. Food-derived peptides are widely used in functional foods due to their low toxicity, ease of digestion and absorption, and potential to improve osteoporosis. This review summarized and discussed methods of diagnosing osteoporosis, treatment approaches, specific peptides as alternatives to conventional drugs, and the laboratory preparation and identification methods of peptides. It was found that peptides interacting with RGD (arginine-glycine-aspartic acid)-binding active sites in integrin could alleviate osteoporosis, analyzed the interaction sites between these osteogenic peptides and integrin, and further discussed their effects on improving osteoporosis. These may provide new insights for rapid screening of osteogenic peptides, and provide a theoretical basis for their application in bone materials and functional foods.

Osteoporosis

As the global population ages, the prevalence of diseases associated with aging, such as diabetes, arthritis, and dementia, also increases ( Li et al., 2021 , Lopes et al., 2022 ). Among these, the increasing incidence of chronic diseases such as osteoporosis have caused a significant societal burden ( Su et al., 2020 ). Osteoporosis affects more than 200 million people worldwide ( Shen et al., 2022 ). By 2030, the number of hip fractures among males are estimated to increase by 51.8% globally, and females are at even higher risk ( Gasparik et al., 2023 ). The increasing incidence of osteoporosis may contribute to a higher risk of fractures and reduced life expectancy, necessitating investigations on the prevention and treatment of this condition.

In the human body, normal bone metabolism involves persistent bone tissue remodeling through osteoblast-dependent bone formation and osteoclast-dependent bone resorption. Enhanced bone resorption leads to reduced bone density, a primary factor in the development of osteoporosis ( Malluche, Davenport, Lima, & Monier-Faugere, 2022 ). Osteoporosis is characterized by reduced bone density, deteriorating bone microstructure, and aggravated bone fragility, which increase the risk of fracture. These changes in bone structure are closely linked to the activities of osteoblasts and osteoclasts: osteoblasts secrete non-collagen proteins to regulate the mineralization of bone matrix, while osteoclasts are responsible for bone resorption ( Kittivanichkul, Watanabe, Nagaoka, & Malaivijitnond, 2016 ). Osteocytes, the most abundant cells in mature bone ( Fig. 1 ), interact with osteoblasts and osteoclasts to influence bone formation and resorption and are closely related to osteoporosis.

Perspectives

The value of food protein digests and bioactive peptides as functional foods in the future cannot be estimated. A healthy diet should contain osteogenic peptides that have been investigated through preclinical research and clinical trials. Prediction of osteogenic peptides directly from enzymatic hydrolysis products has significantly reduced the cost of osteogenic peptides compared to multi-step purification, isolation, screening and identification. Moreover, advanced and powerful technologies, such as mass spectrometry, protein purification, bioinformatics, crystallography, micro-computed tomography, and biofilm interference, are widely utilized to study molecular structure and provide a theoretical basis for understanding the relationship between structure and activity at the molecular level. In this review, the evaluation methods and treatment methods of osteoporosis are reviewed, and it is found that osteopoietic peptides from food sources are a potential source to replace drugs with side effects for osteoporosis treatment. Peptides can improve osteoporosis by interacting with RGD binding sites within integrins, which may be used in future computer simulations to rapidly predict and screen new methods of osteogenic peptides. Taken together, these not only improve the safety of osteoporosis treatment but also reduce the cost of screening osteogenic peptides. This review aims to encourage studies on the structure-activity relationships between osteogenic peptides and integrins that regulate cell adhesion, promoting osteoblast and inhibiting osteoclast proliferation and differentiation. Osteogenic peptides also have the potential for application in the development of bioadhesives for bone materials. Therefore, research ideas for predicting and screening bone-forming active peptides have been summarized, these ideas may lead to the development of bone materials, active drugs that promote bone formation and functional foods.