Extracellular derivatives for bone metabolism

Abstract

Background: Bone metabolism can maintain the normal homeostasis and function of bone tissue. Once the bone metabolism balance is broken, it will cause osteoporosis, osteoarthritis, bone defects, bone tumors, or other bone diseases. However, such orthopedic diseases still have many limitations in clinical treatment, such as drug restrictions, drug tolerance, drug side effects, and implant rejection.

Aim of review: In complex bone therapy and bone regeneration, extracellular derivatives have become a promising research focus to solve the problems of bone metabolic diseases. These derivatives, which include components such as extracellular matrix, growth factors, and extracellular vesicles, have significant therapeutic potential. It has the advantages of good biocompatibility, low immune response, and dynamic demand for bone tissue. The purpose of this review is to provide a comprehensive perspective on extracellular derivatives for bone metabolism and elucidate the intrinsic properties and versatility of extracellular derivatives. Further discussion of them as innovative advanced orthopedic materials for improving the effectiveness of bone therapy and regeneration processes.

Key scientific concepts of review: In this review, we first listed the types and functions of three extracellular derivatives. Then, we discussed the effects of extracellular derivatives of different cell sources on bone metabolism. Subsequently, we collected applications of extracellular derivatives in the treatment of bone metabolic diseases and summarized the advantages and challenges of extracellular derivatives in clinical applications. Finally, we prospected the extracellular derivatives in novel orthopedic materials and clinical applications. We hope that the comprehensive understanding of extracellular derivatives in bone metabolism will provide new solutions to bone diseases.

Keywords: Bone regeneration; Clinical application; Extracellular matrix; Extracellular vesicles; Osteoporosis.

Graphical abstract

Fig. 1

Diagram of the types and structure of extracellular derivatives and bone metabolism. Three main extracellular derivatives: ECM, growth factors, and EVs. The common function of the three is to participate in cell communication and signal transmission in bone metabolism. The difference is that ECM can also provide mechanical properties and signal storage functions for cells and tissues, growth factors can directly act on related cells of bone metabolism, and EVs can carry nucleic acids of source cells. The dynamic balance of bone regeneration and bone resorption maintains a good bone metabolism process, whereas the extracellular derivatives also change when the imbalance occurs, which can regulate bone metabolism through extracellular derivatives. The figure was created with BioRender.com.

Fig. 2

Schematic diagram of the types, generation, and effects of extracellular derivatives. i) The complex network of cells secreting collagen, hyaluronic acid, and proteoglycan into the extracellular space is ECM, which provides structural support, nutrients, and regulating signal pathways for tissues and organs. ii) Growth factors are usually produced by cells in response to stimuli or during specific stages of development or tissue repair. They can be secreted locally or transmitted throughout the body, bind to specific receptors on the cell surface, initiate intracellular signaling cascades, and regulate gene expression, protein synthesis, and cellular response. iii) EVs are formed through the plasma membrane inward budding or outward foaming, resulting in the cell components being encapsulated in EVs. They can carry various bioactive molecules such as nucleic acids, proteins, and lipids from the parent cells. EVs also can be absorbed by the recipient cells through mechanisms such as endocytosis and receptor binding, leading to the transfer of its cargo and subsequent cell function regulation. The figure was created with BioRender.com.

Fig. 3

Diagram of cells associated with bone formation units, bone resorption units, and hematopoietic units involved in bone metabolism. MSCs have multidirectional differentiation potential and can differentiate into osteoblast precursors, chondrocytes, and endothelial cells. Osteoblasts and osteoclasts work in homeostasis to ensure proper bone remodeling. Osteoblasts deposit new bone matrix, while osteoclasts absorb old or damaged bone, and hematopoietic stem cells provide a continuous supply of osteoclast precursors and other blood cell lineages for bone development, repair, and maintenance. Different cells produce their specific extracellular derivatives, and the interaction and communication between cells are strictly regulated and coordinated to maintain bone homeostasis. The figure was created with BioRender.com.

Fig. 4

Schematic diagram of biomaterials prepared by extracellular derivatives for treating bone diseases. The figure was created with BioRender.com.

Fig. 5

Advantages and challenges of extracellular derivative for clinical application. The figure was created with BioRender.com.