Effects of hyperbaric oxygen on gene expressions of procollagen, matrix metalloproteinase and tissue inhibitor of metalloproteinase in injured medial collateral ligament and anterior cruciate ligament

Abstract

Animal experiments were performed to investigate whether and how the administration of hyperbaric oxygen (HBO) affects gene expressions of procollagens, matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in injured medial collateral ligament (MCL) and anterior cruciate ligament (ACL). In 64 Sprague-Dawley rats, the MCL of the left knee was lacerated at the midsubstance, and the ACL of the left knee was lacerated adjacent to the tibial insertion in another 64 rats. Of these, 32 rats with lacerated MCL and 32 rats with lacerated ACL were housed in individual cages at normal atmospheric pressure (Groups MC and AC, respectively), while the remaining 64 rats were exposed to 100% oxygen at 2.5 atmospheres absolute for 2 h for 5 days a week (Groups MH and AH, respectively). Rats were sacrificed at 3, 7, 14 and 28 days postoperatively. After macroscopic examination, bilateral MCLs were harvested from Groups MC and MH, and bilateral ACLs from Groups AC and AH. Total RNA was extracted from each specimen and gene expressions of type I and type III procollagens, MMP-2, -9 and -3, and TIMP-1 and -2 were estimated using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). Macroscopically, lacerated MCL healed by scar tissue formation, the amount of which appeared to be greater in Group MH than in Group MC. In contrast, no lacerated ACLs united, and little, if any, differences were apparent in macroscopic findings between Groups AH and AC. Gene expression of type I procollagen was significantly greater in Group MH than in Group MC at 7 days postoperatively and was also significantly greater in Group AH than in Group AC at 28 days (P<0.05). No significant differences in type III procollagen gene expression were noted between Groups MH and MC or between Groups AH and AC. In addition, no significant differences in gene expressions of MMPs were seen in either ligament, except that gene expression of MMP-13 was significantly lower at 7 days in Group MH than in Group MC (P<0.05). Gene expressions of TIMPs did not differ significantly between Groups MH and MC in each time interval, whereas gene expressions of TIMPs were significantly greater in Group AH than in Group AC at 7, 14 and 28 days for TIMP-1 and at 3, 7 and 14 days for TIMP-2 (P<0.05). RT-PCR results suggested that HBO enhances structural protein synthesis and inhibits degradative processes by enhancing TIMP activities in the lacerated ACL. However, none of the lacerated ACLs united macroscopically despite administration of HBO, indicating that the effect of HBO is insufficient for healing of the injured ACL. If HBO therapy is used as an adjunctive therapy after primary repair of the injured ACL, the success rate of surgery seems likely to be increased.

Hyperbaric Oxygen Treatment Induces a 2-Phase Antinociceptive Response of Unusually Long Duration in Mice

“…It is interesting to note here that the duration of this antinociceptive effect (early-phase antinociception) is a multiple of the 90-min effect observed after a single HBO 2 exposure. This may suggest that HBO 2 treatment induces some type of up-regulation mechanism, which has been reported recently by others3,15,23.…”

Effect of Selective Estrogen Receptor Modulator/Raloxifene Analogue on Proliferation and Collagen Metabolism of Tendon Fibroblast

“…Exposure of fibroblasts to 10 −9 M E 2 and 10 −7 M LY117018 tended to increase the amount of type III collagen and MMP-13 secreted in the culture medium and these effects of E 2 and LY117018 were attenuated by treatment with ICI 182,780 (10 −7 M). degradation [12], alterations in the expression of MMP-13 might indicate that estrogen deficiency retards collagen turnover and that treatment with either E 2 or SERM recovers MMP-13 expression to the premenopausal level. If this is the case in vivo, hormonal alterations after menopause might induce a breakdown in the balance of collagen metabolism and retard remodeling of the tendon ECM, leading to the degradation of tendon properties and structure.…”

“…Homeostasis of these tissues depends on the balance between 180 T. IRIE ET AL the synthetic and degradative activities of tendon fibroblasts [12]. The mechanical properties of these tissues change due to vascular, cellular, and collagen-related alterations, and the loss of elasticity and decrease in the strength of these tissues deteriorate motor function, leading to a decrease in the activities of daily living, especially in senile or postmenopausal people.…”

Comparison between Operative and Non-Operative Treatment of the Medial Collateral Ligament: Histological and Ultrastructural Findings during Early Healing in the Epiligament Tissue in a Rat Knee Model

“…Most studies have reported an insufficient repair process and have tested different treatment regimens, including tissue engineering approaches, non-steroidal anti-inflammatory drugs, local corticosteroids, hyperbaric oxygen, growth factors, ultrasonic or electrical stimulation, laser therapy, and also gene therapy [Ng et al, 2004;Creighton et al, 2005;Chen et al, 2006;Chamberlain et al, 2009]. However, most of the experimental studies on animal models have focused on characterizing only the extracellular matrix in both normal and injured ligaments [Provenzano et al, 2001;Lo et al, 2002;Majima et al, 2006;Tashiro et al, 2006;Woo et al, 2006;Takeyama et al, 2007].…”