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Abstract
Cartilage is a non-innervated and non-vascularized tissue. It is composed of one main cell type, the chondrocyte, which governs homeostasis within the cartilage tissue, but has low metabolic activity. Articular cartilage undergoes substantial stresses that lead to chondral defects, and inevitably osteoarthritis (OA) due to the low intrinsic repair capacity of cartilage. OA remains an incurable degenerative disease. In this context, several dietary supplements have shown promising results, notably in the relief of OA symptoms. In this study, we investigated the effects of collagen hydrolysates derived from fish skin (Promerim®30 and Promerim®60) and fish cartilage (Promerim®40) on the phenotype and metabolism of human articular chondrocytes (HACs). First, we demonstrated the safety of Promerim® hydrolysates on HACs cultured in monolayers. Then we showed that, Promerim® hydrolysates can increase the HAC viability and proliferation, while decreasing HAC SA-β-galactosidase activity. To evaluate the effect of Promerim® on a more relevant model of culture, HAC were cultured as organoids in the presence of Promerim® hydrolysates with or without IL-1β to mimic an OA environment. In such conditions, Promerim® hydrolysates led to a decrease in the transcript levels of some proteases that play a major role in the development of OA, such as Htra1 and metalloproteinase-1. Promerim® hydrolysates downregulated HtrA1 protein expression. In contrast, the treatment of cartilage organoids with Promerim® hydrolysates increased the neosynthesis of type I collagen (Promerim®30, 40 and 60) and type II collagen isoforms (Promerim®30 and 40), the latter being the major characteristic component of the cartilage extracellular matrix. Altogether, our results demonstrate that the use of Promerim® hydrolysates hold promise as complementary dietary supplements in combination with the current classical treatments or as a preventive therapy to delay the occurrence of OA in humans.
Highlights
Articular cartilage (AC) is the tissue that covers the ends of the bones in diarthrodial joints
To evaluate the safety of Promerim® hydrolysates, human articular chondrocytes (HACs) were cultured in monolayer and at 80% confluency were treated with Promerim®30, 40 or 60 at concentrations ranging from 0.1 to 250 μg/mL
We assessed the safety of Promerim® hydrolysates when HACs were cultured in the presence of 2% FCS, used for optimizing the subsequent organoid culture conditions
Summary
Articular cartilage (AC) is the tissue that covers the ends of the bones in diarthrodial joints. AC is mainly composed of an abundant extracellular matrix (ECM) synthesized by a small proportion of chondrocytes (1–3% of the tissue volume) [1,2,3]. The AC ECM contains several collagens and proteoglycans that provide the tissue with resistance to mechanical loads and shear forces. The most abundant collagens are type II (IIB and IIA isoforms), IX and XI collagens, whereas the most abundant proteoglycan is aggrecan [4]. AC resides in a hypoxic environment and has a very low intrinsic capacity for self-repair [5,6,7]. Chondral defects inevitably lead to osteoarthritis (OA) [8]. 300 million people worldwide suffer from OA, including approximately 30.8 million people in the United States and 70 million people in Europe [12,13]
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