Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes

C. H. Lee, Z. H. Wen, Y. C. Chang, S. Y. Huang, C. C. Tang, W. F. Chen, S. P. Hsieh, C. S. Hsieh, Y. H. Jean

Research output: Contribution to journalArticle

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Abstract

Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO4) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA + MgSO4 group (n = 7), the treated knee was injected with 500-μg (0.1-ml) MgSO4 twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO4 group (n = 6), naïve rats received only MgSO4 injections; in the control group (n = 6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO4 on N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular MgSO4 injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO4 treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO4 group as compared to the OA group. Moreover, MgSO4 attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. Conclusions: Our results indicate that local intra-articular administration of MgSO4 following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown

Original languageEnglish
Pages (from-to)1485-1493
Number of pages9
JournalOsteoarthritis and Cartilage
Volume17
Issue number11
DOIs
Publication statusPublished - Nov 2009

Fingerprint

Magnesium Sulfate
Phosphorylation
Nociception
Cell death
Chondrocytes
Osteoarthritis
Magnesium
Rats
Joints
Association reactions
Apoptosis
Hyperalgesia
Cartilage
Collagenases
Intra-Articular Injections
Injections
Knee
Enzyme inhibition
aspartic acid receptor
Sulfates

Keywords

  • Chondrocyte apoptosis
  • Magnesium sulfate
  • NMDA
  • Nociception
  • Osteoarthritis

ASJC Scopus subject areas

  • Biomedical Engineering
  • Orthopedics and Sports Medicine
  • Rheumatology

Cite this

Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception : association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes. / Lee, C. H.; Wen, Z. H.; Chang, Y. C.; Huang, S. Y.; Tang, C. C.; Chen, W. F.; Hsieh, S. P.; Hsieh, C. S.; Jean, Y. H.

In: Osteoarthritis and Cartilage, Vol. 17, No. 11, 11.2009, p. 1485-1493.

Research output: Contribution to journalArticle

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title = "Intra-articular magnesium sulfate (MgSO4) reduces experimental osteoarthritis and nociception: association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes",
abstract = "Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO4) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA + MgSO4 group (n = 7), the treated knee was injected with 500-μg (0.1-ml) MgSO4 twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO4 group (n = 6), na{\"i}ve rats received only MgSO4 injections; in the control group (n = 6), na{\"i}ve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO4 on N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular MgSO4 injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO4 treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO4 group as compared to the OA group. Moreover, MgSO4 attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. Conclusions: Our results indicate that local intra-articular administration of MgSO4 following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown",
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T2 - association with attenuation of N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation and apoptosis in rat chondrocytes

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AU - Wen, Z. H.

AU - Chang, Y. C.

AU - Huang, S. Y.

AU - Tang, C. C.

AU - Chen, W. F.

AU - Hsieh, S. P.

AU - Hsieh, C. S.

AU - Jean, Y. H.

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N2 - Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO4) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA + MgSO4 group (n = 7), the treated knee was injected with 500-μg (0.1-ml) MgSO4 twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO4 group (n = 6), naïve rats received only MgSO4 injections; in the control group (n = 6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO4 on N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular MgSO4 injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO4 treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO4 group as compared to the OA group. Moreover, MgSO4 attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. Conclusions: Our results indicate that local intra-articular administration of MgSO4 following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown

AB - Objective: To study the effects of intra-articular injection of magnesium sulfate (MgSO4) on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods: OA was induced in Wistar rats with intra-articular injection of collagenase (500 U) in the right knee; the left knee was left untreated. In the OA + MgSO4 group (n = 7), the treated knee was injected with 500-μg (0.1-ml) MgSO4 twice a week for 5 consecutive weeks starting at 1 week after collagenase injection; in the OA group (n = 7), the same knee was injected with the same amount of physiological normal saline. In the MgSO4 group (n = 6), naïve rats received only MgSO4 injections; in the control group (n = 6), naïve rats received only physiological normal saline injections. Nociceptive behavior (mechanical allodynia and thermal hyperalgesia) on OA development was measured before and at 1, 2, 4, 6, and 8 weeks after collagenase injection, following which the animals were sacrificed. Gross morphology and histopathology were examined in the femoral condyles, tibial plateau, and synovia. Immunohistochemical analysis was performed to examine the effect of MgSO4 on N-methyl-d-aspartate (NMDA) receptor subunit 1 phosphorylation (p-NR1) and apoptosis in the articular cartilage chondrocytes. Results: OA rats receiving intra-articular MgSO4 injections showed a significantly lower degree of cartilage degeneration than the rats receiving saline injections. MgSO4 treatment also suppressed synovitis. Mechanical allodynia and thermal hyperalgesia showed significant improvement in the OA + MgSO4 group as compared to the OA group. Moreover, MgSO4 attenuated p-NR1 and chondrocyte apoptosis in OA-affected cartilage. Conclusions: Our results indicate that local intra-articular administration of MgSO4 following collagenase injection in an experimental rat OA model (1) modulates chondrocyte metabolism through inhibition of cell NMDA receptor phosphorylation and apoptosis, (2) attenuates the development of OA, and (3) concomitantly reduces nociception. Crown

KW - Chondrocyte apoptosis

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KW - Nociception

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