Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study

Medical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, wheth...

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Main Authors: Jiangyinzi Shang, Sophie Hines, Meagan J. Makarczyk, Hang Lin, MaCalus V. Hogan, Alan Yan
Format: Article
Language:English
Published: MDPI AG 2023-10-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/10/1502
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author Jiangyinzi Shang
Sophie Hines
Meagan J. Makarczyk
Hang Lin
MaCalus V. Hogan
Alan Yan
author_facet Jiangyinzi Shang
Sophie Hines
Meagan J. Makarczyk
Hang Lin
MaCalus V. Hogan
Alan Yan
author_sort Jiangyinzi Shang
collection DOAJ
description Medical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, whether marijuana byproducts can suppress osteoarthritis (OA)-associated cartilage degradation has not been previously reported. In this study, human chondrocytes were isolated from healthy articular cartilage, expanded in vitro, and subjected to pellet culture in a chondrogenic medium to form cartilage tissues. We first examined the influence of marijuana byproducts on normal cartilage by treating chondrocyte-derived tissues with a synthetic cannabinoid agonist, Win-55,212-2 (Win), at different concentrations ranging from 0.01 to 10 µM. After treatment, the tissue phenotype was assessed using glycosaminoglycan (GAG) assay and real-time PCR. Next, cartilage tissues were pre-treated with interleukin-1β (IL-1β) to generate an inflamed phenotype and then cultured with Win to assess its therapeutic potential. The results showed that at concentrations lower than 1 µM, Win treatment did not significantly impair chondrocyte growth or cartilage formation capacity, but at a high level (>10 µM), it remarkably suppressed cell proliferation. Interestingly, under the condition of IL-1β pre-treatment, Win was able to partially preserve the cartilage matrix and decrease the production of interleukin-6, although the protective effect was mild. Taken together, our results indicated that the variable effects of Win on chondrocytes occur in a concentration-dependent manner. Whether cannabinoid derivatives can be used to treat cartilage degradation or can alter other structural changes in OA deserve further investigation.
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spelling doaj.art-b6032204e03242b4ac05c1f05e99e1bd2023-11-19T15:50:09ZengMDPI AGBiomolecules2218-273X2023-10-011310150210.3390/biom13101502Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro StudyJiangyinzi Shang0Sophie Hines1Meagan J. Makarczyk2Hang Lin3MaCalus V. Hogan4Alan Yan5Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USADepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USAMedical marijuana (versus Marijuana derivatives) has been reported to possess analgesic, immunomodulatory, and anti-inflammatory properties. Recent studies in animal models of arthritis showed that cannabinoids, a group of compounds produced from marijuana, may attenuate joint damage. However, whether marijuana byproducts can suppress osteoarthritis (OA)-associated cartilage degradation has not been previously reported. In this study, human chondrocytes were isolated from healthy articular cartilage, expanded in vitro, and subjected to pellet culture in a chondrogenic medium to form cartilage tissues. We first examined the influence of marijuana byproducts on normal cartilage by treating chondrocyte-derived tissues with a synthetic cannabinoid agonist, Win-55,212-2 (Win), at different concentrations ranging from 0.01 to 10 µM. After treatment, the tissue phenotype was assessed using glycosaminoglycan (GAG) assay and real-time PCR. Next, cartilage tissues were pre-treated with interleukin-1β (IL-1β) to generate an inflamed phenotype and then cultured with Win to assess its therapeutic potential. The results showed that at concentrations lower than 1 µM, Win treatment did not significantly impair chondrocyte growth or cartilage formation capacity, but at a high level (>10 µM), it remarkably suppressed cell proliferation. Interestingly, under the condition of IL-1β pre-treatment, Win was able to partially preserve the cartilage matrix and decrease the production of interleukin-6, although the protective effect was mild. Taken together, our results indicated that the variable effects of Win on chondrocytes occur in a concentration-dependent manner. Whether cannabinoid derivatives can be used to treat cartilage degradation or can alter other structural changes in OA deserve further investigation.https://www.mdpi.com/2218-273X/13/10/1502cannabismarijuanaendocannabinoidcannabinoid receptorosteoarthritiscartilage
spellingShingle Jiangyinzi Shang
Sophie Hines
Meagan J. Makarczyk
Hang Lin
MaCalus V. Hogan
Alan Yan
Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
Biomolecules
cannabis
marijuana
endocannabinoid
cannabinoid receptor
osteoarthritis
cartilage
title Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
title_full Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
title_fullStr Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
title_full_unstemmed Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
title_short Influence of the Synthetic Cannabinoid Agonist on Normal and Inflamed Cartilage: An In Vitro Study
title_sort influence of the synthetic cannabinoid agonist on normal and inflamed cartilage an in vitro study
topic cannabis
marijuana
endocannabinoid
cannabinoid receptor
osteoarthritis
cartilage
url https://www.mdpi.com/2218-273X/13/10/1502
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