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dc.contributor.authorGeorge, Kerri L.
dc.contributor.authorSaltman, Laura H.
dc.contributor.authorStein, Gary S.
dc.contributor.authorLian, Jane B.
dc.contributor.authorZurier, Robert B.
dc.date2022-08-11T08:10:57.000
dc.date.accessioned2022-08-23T17:26:22Z
dc.date.available2022-08-23T17:26:22Z
dc.date.issued2008-03-06
dc.date.submitted2011-01-11
dc.identifier.citationJ Cell Physiol. 2008 Mar;214(3):714-20. <a href="http://dx.doi.org/10.1002/jcp.21263">Link to article on publisher's site</a>
dc.identifier.issn0021-9541 (Linking)
dc.identifier.doi10.1002/jcp.21263
dc.identifier.pmid17786950
dc.identifier.urihttp://hdl.handle.net/20.500.14038/49623
dc.description.abstractOral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, prevents joint tissue injury in rats with adjuvant induced arthritis. Because activation of osteoclasts is central to the pathogenesis of bone erosion in patients with rheumatoid arthritis (RA), we investigated the influence of AjA on osteoclast differentiation and survival. Osteoclast cultures were established by stimulation of RAW264.7 cells and primary mouse bone marrow cultures with receptor activator of NF-kappaB ligand (RANKL). Simultaneous addition of AjA (15 and 30 microM) and RANKL to both culture systems significantly suppressed development of multinucleated osteoclasts (osteoclastogenesis) in a dose dependent manner, as determined by quantification of multinuclear, tartrate-resistant acid phosphatase (TRAP)-positive cells. AjA impaired growth of RAW264.7 monocytes and prevented further osteoclast formation in cultures in which osteoclastogenesis had already begun. Reduction by AjA of both monocyte growth and osteoclast formation was associated with apoptosis, assayed by annexin V and propidium iodide staining, and caspase activity. The anti-osteoclastogenic effects of AjA did not require the continuous presence of AjA in the cell cultures. Based on these findings, we propose that AjA or other nonpsychoactive synthetic analogs of Cannabis constituents may be useful therapy for diseases such as RA and osteoporosis in which bone resorption is a central feature.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=17786950&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1002/jcp.21263
dc.subjectAnimals
dc.subjectApoptosis
dc.subjectCannabinoids
dc.subjectCell Culture Techniques
dc.subjectCell Differentiation
dc.subjectCell Proliferation
dc.subjectDose-Response Relationship, Drug
dc.subjectLeukocytes, Mononuclear
dc.subjectMacrophages
dc.subjectMice
dc.subjectMice, Inbred BALB C
dc.subjectOsteoclasts
dc.subjectPsychotropic Drugs
dc.subjectRANK Ligand
dc.subjectStem Cells
dc.subjectTetrahydrocannabinol
dc.subjectCell Biology
dc.titleAjulemic acid, a nonpsychoactive cannabinoid acid, suppresses osteoclastogenesis in mononuclear precursor cells and induces apoptosis in mature osteoclast-like cells
dc.typeJournal Article
dc.source.journaltitleJournal of cellular physiology
dc.source.volume214
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/stein/51
dc.identifier.contextkey1724091
html.description.abstract<p>Oral administration of ajulemic acid (AjA), a cannabinoid acid devoid of psychoactivity, prevents joint tissue injury in rats with adjuvant induced arthritis. Because activation of osteoclasts is central to the pathogenesis of bone erosion in patients with rheumatoid arthritis (RA), we investigated the influence of AjA on osteoclast differentiation and survival. Osteoclast cultures were established by stimulation of RAW264.7 cells and primary mouse bone marrow cultures with receptor activator of NF-kappaB ligand (RANKL). Simultaneous addition of AjA (15 and 30 microM) and RANKL to both culture systems significantly suppressed development of multinucleated osteoclasts (osteoclastogenesis) in a dose dependent manner, as determined by quantification of multinuclear, tartrate-resistant acid phosphatase (TRAP)-positive cells. AjA impaired growth of RAW264.7 monocytes and prevented further osteoclast formation in cultures in which osteoclastogenesis had already begun. Reduction by AjA of both monocyte growth and osteoclast formation was associated with apoptosis, assayed by annexin V and propidium iodide staining, and caspase activity. The anti-osteoclastogenic effects of AjA did not require the continuous presence of AjA in the cell cultures. Based on these findings, we propose that AjA or other nonpsychoactive synthetic analogs of Cannabis constituents may be useful therapy for diseases such as RA and osteoporosis in which bone resorption is a central feature.</p>
dc.identifier.submissionpathstein/51
dc.contributor.departmentDepartment of Cell Biology
dc.contributor.departmentDepartment of Medicine, Division of Rheumatology
dc.source.pages714-20


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