Reduction of Infection Stones in Rats by Combined Antibiotic and Phosphocitrate Therapy

Salus, Juraj; Thomson, R. M.; Rees, Beth; Shankar, Ravi

doi:10.1016/s0022-5347(17)41927-6

Cited by 20 publications

(4 citation statements)

References 11 publications

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“…The AHA primarily acts as a urease inhibitor, which may disrupt the struvite growth and formation directly through the interference with the molecular growth processes on crystal surface. Phosphocitrate was reported to inhibit in vivo formation of struvite [44]. Crystal growth studies and molecular modeling results indicate strong affinity of phosphorcitrate to (1 0 1) faces of struvite [45].…”

Section: Growth Inhibition Studiesmentioning

confidence: 99%

In vitro crystallization, characterization and growth-inhibition study of urinary type struvite crystals

Chauhan

Joshi

2013

Journal of Crystal Growth

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Section: Growth Inhibition Studiesmentioning

confidence: 99%

In vitro crystallization, characterization and growth-inhibition study of urinary type struvite crystals

Chauhan

Joshi

2013

Journal of Crystal Growth

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“…Hartley guinea pigs have been widely used to study the pathogenesis of OA and test potential OA disease‐modifying drugs. Phosphocitrate (PC) is a powerful calcification inhibitor, which prevents soft tissue calcification, and displays no toxic side effect in rats in doses up to 150 μmol/kg/day . PC also inhibits crystal‐induced cell membrane damages, mitogenesis, expression of extracellular matrix‐degrading enzymes, and crystal‐induced cell death .…”

mentioning

confidence: 99%

Biological effects and osteoarthritic disease‐modifying activity of small molecule CM‐01

Sun

Roberts

Mauerhan

et al. 2017

Journal Orthopaedic Research

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Phosphocitrate inhibits cartilage degeneration, however, the prospect of phosphocitrate as an oral disease modifying drug might be limited. The purpose of this study was to investigate the biological effects and disease-modifying activity of a phosphocitrate "analog," CM-01 (Carolinas Molecule-01), and test the hypothesis that CM-01 is a disease modifying drug for osteoarthritis therapy. The effects of CM-01 on calcium crystal-induced expression of matrix metalloproteinase-1 and interleukin-1 beta, cell-mediated calcification and production of proteoglycan by chondrocytes were examined in cell cultures. Disease-modifying activity was examined using Hartley guinea pig model of posttraumatic osteoarthritis. Cartilage degeneration in untreated and CM-01 treated guinea pigs was examined with Indian ink and Safranin-O-fast green. Levels of matrix metalloproteinase-13, ADAM metallopeptidase with thrombospondin type 1 motif 5, chemokine (C-C motif) ligand 5, and cyclooxygenase 2 were examined with immunostaining. CM-01 inhibited crystal-induced expression of matrix metalloproteinase-1 and interleukin-1β, reduced cell-mediated calcification, and stimulated the production of proteoglycan by chondrocytes. In Hartley guinea pigs, CM-01 not only reduced damages in articular surface but also reduced resorption of calcified zone cartilage. The reduction in cartilage degeneration was accompanied by decreased levels of matrix metalloproteinase-13, ADAM metallopeptidase with thrombospondin type 1 motif 5, chemokine (C-C motif) ligand 5 and cyclooxygenase 2. These findings confirmed that CM-01 is a promising candidate to be tested as an oral drug for human OA therapy. CM-01 exerted its disease-modifying activity on osteoarthritis, in part, by inhibiting the production of matrix-degrading enzymes and a molecular program resembling the endochondral pathway of ossification. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:309-317, 2018.

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“…It prevents soft-tissue calcification and has been reported to have no toxic side effect in rats in doses up to 150 µmol/kg/day. 25 - 27 We recently demonstrated that intraperitoneal injection of PC and PC analogues inhibited cartilage degeneration in Hartley guinea pig models of post-traumatic OA. 28 , 29 However, the prospect of PC as an oral disease-modifying drug for human OA therapy might be limited because PC contains a phosphate-oxygen atom-carbon (P-O-C) bond and five negative charges.…”

Section: Introductionmentioning

confidence: 99%

Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea pigs

Sun

Kiraly

Sun

et al. 2018

Bone & Joint Research

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ObjectivesThe objectives of this study were: 1) to examine osteophyte formation, subchondral bone advance, and bone marrow lesions (BMLs) in osteoarthritis (OA)-prone Hartley guinea pigs; and 2) to assess the disease-modifying activity of an orally administered phosphocitrate ‘analogue’, Carolinas Molecule-01 (CM-01).MethodsYoung Hartley guinea pigs were divided into two groups. The first group (n = 12) had drinking water and the second group (n = 9) had drinking water containing CM-01. Three guinea pigs in each group were euthanized at age six, 12, and 18 months, respectively. Three guinea pigs in the first group were euthanized aged three months as baseline control. Radiological, histological, and immunochemical examinations were performed to assess cartilage degeneration, osteophyte formation, subchondral bone advance, BMLs, and the levels of matrix metalloproteinse-13 (MMP13) protein expression in the knee joints of hind limbs.ResultsIn addition to cartilage degeneration, osteophytes, subchondral bone advance, and BMLs increased with age. Subchondral bone advance was observed as early as six months, whereas BMLs and osteophytes were both observed mainly at 12 and 18 months. Fibrotic BMLs were found mostly underneath the degenerated cartilage on the medial side. In contrast, necrotic BMLs were found almost exclusively in the interspinous region. Orally administered CM-01 decreased all of these pathological changes and reduced the levels of MMP13 expression.ConclusionSubchondral bone may play a role in cartilage degeneration. Subchondral bone changes are early events; formation of osteophytes and BMLs are later events in the OA disease process. Carolinas Molecule-01 is a promising small molecule candidate to be tested as an oral disease-modifying drug for human OA therapy.Cite this article: Y. Sun, A. J. Kiraly, A. R. Sun, M. Cox, D. R. Mauerhan, E. N. Hanley Jr. Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea pigs. Bone Joint Res 2018;7:157–165. DOI:10.1302/2046-3758.72.BJR-2017-0253.

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Reduction of Infection Stones in Rats by Combined Antibiotic and Phosphocitrate Therapy

Cited by 20 publications

References 11 publications

In vitro crystallization, characterization and growth-inhibition study of urinary type struvite crystals

In vitro crystallization, characterization and growth-inhibition study of urinary type struvite crystals

Biological effects and osteoarthritic disease‐modifying activity of small molecule CM‐01

Effects of a phosphocitrate analogue on osteophyte, subchondral bone advance, and bone marrow lesions in Hartley guinea pigs

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