Tissue Engineering of Cartilage; Can Cannabinoids Help?

Abstract

This review discusses the role of the cannabinoid system in cartilage tissue and endeavors to establish if targeting the cannabinoid system has potential in mesenchymal stem cell based tissue-engineered cartilage repair strategies. The review discusses the potential of cannabinoids to protect against the degradation of cartilage in inflamed arthritic joints and the influence of cannabinoids on the chondrocyte precursors, mesenchymal stem cells (MSCs). We provide experimental evidence to show that activation of the cannabinoid system enhances the survival, migration and chondrogenic differentiation of MSCs, which are three major tenets behind the success of a cell-based tissue-engineered cartilage repair strategy. These findings highlight the potential for cannabinoids to provide a dual function by acting as anti-inflammatory agents as well as regulators of MSC biology in order to enhance tissue engineering strategies aimed at cartilage repair.

The Cannabinoid Receptor Type 1 Is Essential for Mesenchymal Stem Cell Survival and Differentiation: Implications for Bone Health

“…Thus, Δ 9 -THC exposure may lead to a decreased ability of MSCs to differentiate into their mature bone forming progeny due to a lack of cell viability at early stages of osteogenesis which could inturn impact upon the osteogenic potential of MSCs (supplemental Figure  4). Furthermore we conclude that this effect is specific to a long-term treatment with Δ 9 -THC as we have previously published observations showing no deleterious effects following an acute 24-hour Δ 9 -THC (1  μ M) treatment [29]. This indicates that a long-term exposure to Δ 9 -THC may have a negative effect on bone health possibly due to exogenous agonist-induced blockade of CB 1 receptor activation by endocannabinoids.…”

“…Furthermore, they showed that increased CB 1 receptor expression enhanced the efficacy of cannabinoids to regulate the prosurvival AKT pathway whilst low levels of CB 1 receptor expression lead only to the activation of ERK [28]. Furthermore, we have previously shown that activation of the cannabinoid system enhances the survival, migration, and chondrogenic differentiation of MSCs, which are the three key points that determine the success of cell-based tissue-engineered repair strategies [29]. Interestingly, Idris et al [13] suggest that normal bone formation in CB 1 receptor knock-out mice can be maintained by alternative signalling pathways; however, with increasing age these compensatory mechanisms fail leading to decreased bone formation.…”

The effect of hydroalcoholic extract of Cannabis Sativa on morphology and growth of bone marrow mesenchymal stem cells in rat

“…There is a consensus in all studies conducted on the effect of cannabis on the induction of apoptosis, but all have overlooked the role of the dose (2,3,5,7,11,21,22). But some people have said that the delta-9-tetrahydrocannabinol in the extract acts as an antioxidant for cell viability, while at the same time high concentrations of this substance cause toxicity and increase apoptosis (9).…”

Platelet‐rich plasma loaded in situ‐formed hydrogel enhances hyaline cartilage regeneration by CB1 upregulation

“…Cannabinoids (CBs) have been reported to have analgesic, anti‐inflammatory, and immunosuppressive effects in animal models of arthritis 45. These positive influences help protect against cartilage degradation in inflamed arthritic joints and osteoarthritis 46, 47. Chondrocytes maintain cartilage tissue homeostasis, sustaining the crucial balance between the rate of biosynthesis and incorporation of matrix components, and the rate of their degradation and subsequent loss from the cartilage into the synovial fluid 48.…”