Functional Duality of Chondrocyte Hypertrophy and Biomedical Application Trends in Osteoarthritis

Abstract

Chondrocyte hypertrophy is one of the key indicators in the progression of osteoarthritis (OA). However, compared with other OA indications, such as cartilage collapse, sclerosis, inflammation, and protease activation, the mechanisms by which chondrocyte hypertrophy contributes to OA remain elusive. As the pathological processes in the OA cartilage microenvironment, such as the alterations in the extracellular matrix, are initiated and dictated by the physiological state of the chondrocytes, in-depth knowledge of chondrocyte hypertrophy is necessary to enhance our understanding of the disease pathology and develop therapeutic agents. Chondrocyte hypertrophy is a factor that induces OA progression; it is also a crucial factor in the endochondral ossification. This review elaborates on this dual functionality of chondrocyte hypertrophy in OA progression and endochondral ossification through a description of the characteristics of various genes and signaling, their mechanism, and their distinguishable physiological effects. Chondrocyte hypertrophy in OA progression leads to a decrease in chondrogenic genes and destruction of cartilage tissue. However, in endochondral ossification, it represents an intermediate stage at the process of differentiation of chondrocytes into osteogenic cells. In addition, this review describes the current therapeutic strategies and their mechanisms, involving genes, proteins, cytokines, small molecules, three-dimensional environments, or exosomes, against the OA induced by chondrocyte hypertrophy. Finally, this review proposes that the contrasting roles of chondrocyte hypertrophy are essential for both OA progression and endochondral ossification, and that this cellular process may be targeted to develop OA therapeutics.

In Vitro Study of Licorice on IL-1β-Induced Chondrocytes and In Silico Approach for Osteoarthritis

“…Further study is needed to fully understand the active components in WG that synergistically act on chondrocyte hypertrophy related OA. However, hypertrophy involves morphologic changes such as enlargement of cells with an increase in apoptotic rate [81]. An in vivo study with morphological evidence may have strengthened our results.…”

Chondrocyte Hypertrophy in Osteoarthritis: Mechanistic Studies and Models for the Identification of New Therapeutic Strategies

“…Several reviews have highlighted the similarity of chondrocyte hypertrophy observed in OA and transient cartilage differentiation [ 8 , 28 , 29 ]; thus, in this article, we will only briefly discuss the resemblance of these two processes.…”

Spatiotemporal Modulated Scaffold for Endogenous Bone Regeneration via Harnessing Sequentially Released Guiding Signals

“…Angiogenesis plays a crucial role in initiating chondrocyte hypertrophy; therefore, the timely and controlled delivery of bioactive factors to promote vascularization is essential for this process. − However, direct loading of water-soluble compounds into hydrogels often results in a burst release that is difficult to synchronize with the spatiotemporal rhythm of ECO . To address this challenge, biodegradable microspheres (termed as M) made of aliphatic polyesters, such as poly­(lactide- co -glycolide) (PLGA), have been extensively studied as drug carriers in various biomedical applications, offering sustained release capabilities .…”