Peptides for Targeting Chondrogenic Induction and Cartilage Regeneration in Osteoarthritis

Abstract

Objects: Osteoarthritis (OA) is a widespread degenerative joint condition commonly occurring in older adults. Currently, no disease-modifying drugs are available, and safety concerns associated with commonly used traditional medications have been identified. In this review, a significant portion of research in this field is concentrated on cartilage, aiming to discover methods to halt cartilage breakdown or facilitate cartilage repair.

Methods: Researchers have mainly investigated the cartilage, seeking methods to promote its repair. This review focuses on peptide-based molecules known for their ability to selectively bind to growth factor cytokines and components of the cartilage extracellular matrix.

Results: Chondroinductive peptides, synthetically producible, boast superior reproducibility, stability, modifiability, and yield efficiency over natural biomaterials. This review outlines a chondroinductive peptide design, molecular mechanisms, and their application in cartilage tissue engineering and also compares their efficacy in chondrogenesis in vitro and in vivo.

Conclusions: In this paper, we will summarize the application of peptides engineered to regenerate cartilage by acting as scaffolds, functional molecules, or both and discuss additional possibilities for peptides. This review article provides an overview of our current understanding of chondroinductive peptides for treating OA-affected cartilage and explores the delivery systems used for regeneration. These advancements may hold promise for enhancing or even replacing current treatment methodologies.

Keywords: chondrogenic induction; osteoarthritis; peptide.

Figure 1.

Current cellular-based strategies employed for cartilage regeneration employ various approaches to promote tissue repair and regeneration. Cellular-based strategies for cartilage regeneration aim to increase the population of cells with the ability to initiate or engage in tissue regeneration. These methods typically prioritize either the recruitment of progenitor cells or the enhancement of chondrocyte density. Recruitment strategies involve techniques such as microfracture, aimed at stimulating the migration of progenitor cells from the bone marrow to the injury site, or exosome delivery to attract nearby progenitor cells. Once recruited, these progenitor cells play a crucial role in cartilage repair by modulating inflammatory responses and promoting chondrogenesis through paracrine signaling, potentially undergoing direct differentiation into chondrocytes. Alternatively, chondrocyte enrichment strategies include procedures such as autologous chondrocyte implantation or matrix-assisted autologous chondrocyte implantation, which are often complemented by agents targeting cellular senescence. Moreover, peptide-based approaches for cartilage regeneration are hypothesized to function by promoting chondrogenesis in activated or regenerating states, enhancing cell viability, or inducing the differentiation of chondrocytes derived from MSCs. The carrier strategy incorporates organic compounds, including chitosan, poly (lactic-co-glycolic) acid (PLGA), HA, and polyester amide (PEA), to improve peptide stability and facilitate delivery.

Figure 2.

Role of peptides in the management of osteoarthritic joints after treatment. Peptides play a crucial role in the treatment of osteoarthritic joints. In a healthy joint, peptides promote cartilage regeneration triggered by mechanical loading, thereby preserving the differentiated chondrocyte phenotype. Conversely, in an osteoarthritic joint, various damaged cartilage phenotypes are observed, accompanied by alterations in chondrocytes. These signals of damage lead to osteophyte formation, chondrocyte hypertrophy, synovial inflammation, increased bone turnover, and the degradation of articular cartilage. Furthermore, the presence of inflammatory cytokines and changes in the cartilage microenvironment exacerbate the propensity of articular chondrocytes toward hypertrophy.

Figure 3.

Schematic of the role of peptides in chondrogenesis. The diagram depicts the category of chondroinductive peptides, detailing their molecular mechanisms and parameters for assessing their in vitro and in vivo efficacies. Specifically, peptides derived from BMP signaling, namely CK2.1 peptide, BMP peptide, and B2A peptide, are shown. These peptides operate by activating BMP signaling, thereby promoting the induction of chondrogenesis in MSCs or chondrocytes. BMP: bone morphogenetic protein; TGF-β: transforming growth factor-β; ECM: extracellular matrix; CMP: collagen mimetic peptide; LPP: link protein N-terminal peptide.