Evaluation of unsulfated biotechnological chondroitin in a knee osteoarthritis mouse model as a potential novel functional ingredient in nutraceuticals and pharmaceuticals

Abstract

Osteoarthritis is a very disabling disease that can be treated with both non-pharmacological and pharmacological approaches. In the last years, pharmaceutical-grade chondroitin sulfate (CS) and glucosamine emerged as symptomatic slow-acting molecules, effective in pain reduction and improved function in patients affected by osteoarthritis. CS is a sulfated glycosaminoglycan that is currently produced mainly by extraction from animal tissues, and it is commercialized as a pharmaceutical-grade ingredient and/or food supplement. However, public concern on animal product derivatives has prompted the search for alternative non-extractive production routes. Thus, different approaches were established to obtain animal-free natural identical CS. On the other hand, the unsulfated chondroitin, which can be obtained via biotechnological processes, demonstrated promising anti-inflammatory properties in vitro, in chondrocytes isolated from osteoarthritic patients. Therefore, the aim of this study was to explore the potential of chondroitin, with respect to the better-known CS, in an in vivo mouse model of knee osteoarthritis. Results indicate that the treatment with biotechnological chondroitin (BC), similarly to CS, significantly reduced the severity of mechanical allodynia in an MIA-induced osteoarthritic mouse model. Decreased cartilage damage and a reduction of inflammation- and pain-related biochemical markers were also observed. Overall, our data support a beneficial activity of biotechnological unsulfated chondroitin in the osteoarthritis model tested, thus suggesting BC as a potential functional ingredient in pharmaceuticals and nutraceuticals with the advantage of avoiding animal tissue extraction.

Hyaluronic Acid-Based Injective Medical Devices: In Vitro Characterization of Novel Formulations Containing Biofermentative Unsulfated Chondroitin or Extractive Sulfated One with Cyclodextrins

“…In recent times, scientific investigations have suggested that CS, alone or in combination with other GAGs, may enhance chondrocyte metabolism, counteract the inflammatory process, and down-regulate the degradative enzymes [20,37]. In this context, the biological properties of BC have lately been tested in an OA animal model [43]. Thus, Cimini et al [43] displayed that BC was as effective in reducing pain and affecting different specific biomarkers related to the inflammatory/degradation progression as CS in an OA mice model, highlighting the possibility of being able to replace extractive chondroitin with the biotechnological one.…”

Hedgehog Signaling Controls Chondrogenesis and Ectopic Bone Formation via the Yap-Ihh Axis

“…Exploring additional methods to treat chondrocyte-related diseases is crucial due to the significant medical challenge posed by abnormal chondrogenesis and the defects observed in conditions like osteoarthritis, which currently have limited treatment options. Recent studies have explored the potential of biotechnological chondroitin (BC) as an alternative to traditional chondroitin sulfate (CS) for treating osteoarthritis [ 44 ]. The results indicate that BC, akin to CS, effectively reduces mechanical allodynia, decreases cartilage damage, and attenuates inflammation- and pain-related biochemical markers in an osteoarthritic mouse model induced by MIA (Monosodium Iodoacetate).…”

Chondroitin sulfate supplementation improves clinical outcomes in a murine model of necrotizing enterocolitis

“…Each day, formula was made based on daily weights and the caloric needs of the pups from the batch stock and supplemented with 0.008 mg/g of Lipopolysaccharide (LPS) isolated from Escherichia Coli O111:B4 (cat # L4391, Sigma‐Aldrich Company, St. Louis, MO). Those in the group to receive chondroitin sulfate, had their formula supplemented to receive 0.2 mg/g chondroitin sulfate daily (Cimini et al, 2022 ; Gao et al, 2022 ; Qi et al, 2021 ; Singh et al, 2021 ; Song et al, 2017 ). Experimental pups were gavage fed a hyper‐concentrated formula (300 kcal/kg/day) three times per day using a 1.9 French catheter.…”

“…A certificate of analysis was provided by the company for the lot number used in these experiments. The dose of chondroitin sulfate was determined by a literature search of chondroitin sulfate doses in different rodent models of disease that all used a dose of 200 mg/kg for beneficial therapeutic effects (Cimini et al, 2022 ; Gao et al, 2022 ; Qi et al, 2021 ; Singh et al, 2021 ; Song et al, 2017 ).…”