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Orthopaedic Proceedings
Vol. 102-B, Issue SUPP_6 | Pages 83 - 83
1 Jul 2020
Yao H Xu J Qin L Zheng N Wang J Ho KW
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Previous study reported that intra-articular injection of MgSO4 could alleviate pain related behaviors in a collagenase induced OA model in rats. It provided us a good description on the potential of Mg2+ in OA treatment. However, the specific efficiency of Mg2+ on OA needs to be further explored and confirmed. The underlying mechanisms should be elucidated as well. Increasing attention has been paid on existence of synovial fluid MSCs (SF-MSCs) (not culture expanded) which may participate in endogenous reparative capabilities of the joint. On the other hand, previous studies demonstrated that Mg2+ not only promoted the expression of integrins but also enhanced the strength of fibronectin-integrin bonds that indicated the promotive effect of Mg2+ on cell adhesion, moreover, Mg2+ was proved could enhance chondrogenic differentiation of synovial membrane derived MSCs by modulating integrins. Based on these evidence, we hypothesize herein intra-articular injection of Mg2+ can attenuate cartilage degeneration in OA rat through modulating the biological behavior of SF-MSCs.

Human and rat SF-MSCs were collected after obtaining Experimental Ethics approval. The biological behaviors of both human and rat SF-MSCs including multiple differentiation, adhesion, colony forming, proliferation, etc. were determined in vitro in presence or absence of Mg2+ (10 mmol/L). Male SD rats (body weight: 450–500 g) were used to establish anterior cruciate ligament transection and partial medial meniscectomy (ACLT+PMM) OA models. The rats received ACLT+PMM were randomly divided into saline (control) group and MgCl2 (0.5 mol/L) group (n=6 per group). Intra-articular injection was performed on week 4 post-operation, twice per week for two weeks. Knee samples were harvested on week 2, 4, 8, 12 and 16 after injection for histological analysis for assessing the progression of OA. On week 2 and 4 after injection, the rat SF-MSCs were also isolated before the rats were sacrificed for assessing the abilities of chondrogenic differentiation, colony forming and adhesion in vitro. Statistical analysis was done using Graphpad Prism 6.01. Unpaired t test was used to compare the difference between groups. Significant difference was determined at P < 0 .05.

The adhesion and chondrogenic differentiation ability of both human and rat SF-MSCs were significantly enhanced by Mg2+ (10 mmol/L) supplementation in vitro. However, no significant effects of Mg2+ (10 mmol/L) on the osteogenic and adipogenic differentiation as well as the colony forming and proliferation. In the animal study, histological analysis by Saffranin O and Toluidine Blue indicated the cartilage degeneration was significantly alleviated by intra-articular injection of Mg2+, in addition, the expression of Col2 in cartilage was also increased in MgCl2 group with respect to control group indicated by immunohistochemistry. Moreover, the OARSI scoring was decreased in MgCl2 group as well. Histological analysis and RT-qPCR indicated that the chondrogenic differentiation of SF-MSCs isolated from Mg2+ treated rats were significantly enhanced compare to control group.

In the current study, we have provided direct evidence supporting that Mg2+ attenuated the progression of OA. Except for the effect of Mg2+ on preventing cartilage degeneration had been demonstrated in this study, for the first time, we demonstrated the promoting effect of Mg2+ on adhesion and chondrogenic differentiation of endogenous SF-MSCs within knee joint that may favorite cartilage repair. We have confirmed that the anti-osteoarthritic effect of Mg2+ involves the multiple actions which refer to prevent cartilage degeneration plus enhance the adhesion and chondrogenic differentiation of SF-MSCs in knee joint to attenuate the progression of OA. These multiple actions of Mg2+ may be more advantage than traditional products. Besides, this simple, widely available and inexpensive administration of Mg2+ has the potential on reducing the massive heath economic burden of OA. However, the current data just provided a very basic concept, the exact functions and underlying mechanisms of Mg2+ on attenuating OA progression still need to be further explored both in vitro and in vivo. Formula of Mg2+ containing solution also need to be optimized, for example, a sustained and controlled release delivery system need to be developed for improving the long-term efficacy.


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 262 - 262
1 Nov 2002
Negishi T Ozeki S Yao H Nohara Y
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Introduction: Functional knee braces are commonly used after ACL reconstruction surgery. However, the study to evaluate the contributions of the knee brace is a few. We investigated the effects of knee brace prospectively.

Methods: From 1993 to 1996, forty eight patients with 48 knees were treated with autogenous ACL reconstruction. The patients were randomly divided to two groups; twenty five patients (group B) used knee brace for one year and the other 23 patients (group NB) were free from bracing. Forty two patients were followed over two years. The averaged follow-up period was 27 mouths and the averaged age at surgery was 24.5 years. The semitendinosus and the gracilis tendon in the contralateral side were used to make triple looped (six strands) substitute. Bone tunnels were made at the appropriate site using inside-out technique under arthroscopy assistance. Polyester meshes were connected to the substitute and fixed to the tibia and femur with staples after grafting through the bone tunnels. The same rehabilitation protocol was used for both patients group. Functional outcomes were evaluated with IKDC score.

Results: The rate of category A, B ,C and D in the group B were 52%, 44%, 4% and 0%. Those in the group NB were 65%, 26%, 9% and 0% respectively. There is not any Statistically significant difference between the two groups.

The joint stability were measured with stress x-p using TELOS device. The anterior displacement ratio improved from 73±4.9%(mean ±sd) to 64±4.6% in group B, and it also improved from 72±4.0% to 62±2.9% in group NB. Statistically significant improvements were obtained after surgery in both the two groups, however, no statistically significant difference of stability were found between the two groups.

Conclusion: These results suggest that the functional knee brace is not indispensable when the hamstring substitute is used for ACL reconstruction with secure fixation methods.