Aims

The purpose of our study was to determine whether mesenchymal stem cells (MSCs) are an effective and safe therapeutic agent for the treatment of knee osteoarthritis (OA), owing to their cartilage regeneration potential.

Osteoporosis (OP) is a chronic metabolic bone disease characterized by the decrease of bone tissue per unit volume under the combined action of genetic and environmental factors, which leads to the decrease of bone strength, makes the bone brittle, and raises the possibility of bone fracture. However, the exact mechanism that determines the progression of OP remains to be underlined. There are hundreds of trillions of symbiotic bacteria living in the human gut, which have a mutually beneficial symbiotic relationship with the human body that helps to maintain human health. With the development of modern high-throughput sequencing (HTS) platforms, there has been growing evidence that the gut microbiome may play an important role in the programming of bone metabolism. In the present review, we discuss the potential mechanisms of the gut microbiome in the development of OP, such as alterations of bone metabolism, bone mineral absorption, and immune regulation. The potential of gut microbiome-targeted strategies in the prevention and treatment of OP was also evaluated.

Cite this article: Bone Joint Res 2020;9(8):524–530.

Total Knee Arthroplasty (TKA) patients may present with effusion, pain, stiffness and functional impairment. A positive metal hypersensitivity (positive LTT) may be an indication for a revision surgery with a custom-made implant devoid of any hypersensitivity-related metal or an implant with the least possible ion content of the metal hypersensitivity, if no custom-made is available. The purpose of the current study is to assess the prevalence of metal hypersensitivity in subjects requiring a primary TKA and assess their early functional outcomes.

We are recruiting 660 subjects admitted for TKA. Subjects are randomly assigned to 2 groups: oxidized zirconium implant group or cobalt-chrome implant group. Functional outcomes and quality of life (QoL) are measured pre operatively, 3, 6 and 12 months post operatively with WHOQOL-BREF (domain1-Physical Health, domain 2- Psychological, domain 3- Social relationships, domain 4-Environment), KSS, KOOS and pain Visual Analog Scale (VAS). LTT and metal ions are evaluated pre operatively and 12 months post-surgery.

One hundred-sixty patients, 98 women, were enrolled in the study. Mean age was 65.6±8.9. Mean follow up (FU) was 7.1±3.8 months. Eighty-one (50.6%) were randomised in the cobalt-chrome group. Infection rate was 1.9%, one patient required debridement. Three patients (1.9%) presented with contracture at three months FU. At 12 months, WHOQOL-BREF domain 1, 2 and 4 improved significantly (p0,05).

Overall, all 160 patients improved their functional outcomes and QoL. At 12 months, VAS scores decreased from 7±2.06 at baseline to 1.95±2.79. Furthermore, the high prevalence of positive LTT (27/65) do not seem to affect early functional outcomes and QoL on patients that may have received a potential implant with hypersensitivity (18/27).

Total joint arthroplasty has proven to be efficient to relieve pain and regain mobility. In fact, most patients undergoing a total knee arthroplasty (TKA) are satisfied with their surgery (80 to 90%), yet 4 to 7% still complain of unexplainable pain and stiffness. Several authors have proposed that reactivity to the implant could explain this phenomenon. Still, no strong evidence supports this theory as of today. We aimed to determine the prevalence of metal and cement hypersensitivity in a cohort of patients with unexplained pain and stiffness after TKA.

We retrieved data for a group of patients presenting unexplained pain and stiffness. We excluded all other potential known causes of pain. All patients were tested with a Lymphocyte Transformation Test from whole blood taps. We analysed data of hypersensitivity to metals (alloy particles of titanium and cobalt, aluminum, cobalt, nickel, zirconium, vanadium, molybdenum, cobalt, chromium and iron) and PMMA cement (bone cement monomer and particles).

Fifty-three patients underwent a LTT for unexplained pain and stiffness after total knee arthroplasty between May 2012 and May 2015. The cohort consisted of 26 men and 27 women with a mean age of 66.3(±8.0) years. Six patients had no hypersensitivity (11.3%), leaving 88.7% of the cohort with hypersensitivity to metal and/or cement. Almost half the cohort of patients tested for PMMA was hypersensitive to cement (44.0%). The most common metal hypersensitivity was nickel (69.8%). Twelve patients presented sensitivity to only one metal (22.6%), whereas 35 patients were hypersensitive to more than one metal (66.0%). Eleven patients had revision surgery with a hypoallergenic prosthesis. Patients reported a significant diminution of pain as well as better knee function compared to preoperative status as early as 6 weeks postop, although some reported residual stiffness.

The results of this study suggest that metal and/or cement hypersensitivity could play a role in cases of total knee arthroplasty with unexplained pain and stiffness. Randomised controlled clinical trials on the subject will be initiated by our team to further investigate this phenomenon.

Summary

Collagen scaffolds loaded with mesenchymal stem cells accelerate neurological recovery in rat spinal hemisection.

Summary Statement

Collagen scaffolds modified with collagen-binding bFGF promotes the neural regeneration in the rat hemisected spinal cord injury model.

We demonstrated for the first time that HNE, a lipid peroxidation end product, plays a role in osteoarthritic (OA) cartilage degradation. The level of HNE/protein adducts increased in synovial fluids from OA patients and in cellular extracts of OA chondrocytes treated with free radicals donors (H2O2 or SIN). We have found that HNE induces MMP-13 synthesis and activity but in contrast inhibits type II collagen and TIMP-1 synthesis. By immunoprecipitation approach, we demonstrated the formation of HNE/type II collagen adducts in OA cartilage and their increased level in the presence of H2O2 or SIN.

To investigate the role of peroxidation end product, 4-hydroxynonenal (HNE), in osteoarthritic (OA) cartilage degradation.

Total HNE/protein adducts were quantified in synovial fluids or in cellular extracts of chondrocytes using a house Elisa. The formation of HNE/type II collagen adducts was analysed by immunoprecipitation. Type II collagen synthesis was analysed by Western blotting. MMP-13 activity and synthesis as well as TIMP-1 synthesis were measured by commercial kits.

Our data show that the level of HNE/protein adducts markedly increased in OA synovial fluids compared to normal subjects and in cellular extracts of OA chondrocytes treated with free radicals donors (H2O2 or SIN) compared to untreated cells. Using an immunoprecipitation approach, we demonstrated the formation of HNE/type II collagen adducts in OA cartilage and their increased level in the presence of H2O2 or SIN. Furthermore, we find that HNE induces MMP-13 synthesis and activity in a dose-dependent manner, but in contrast, inhibits type II collagen and TIMP-1 synthesis. Interestingly, HNE was proved to exert a dual effect in vitro, activating proMMP-13 at low molar ratio (MR~100:1) and inhibiting active MMP-13 at high molar ratio (MR > 1000:1).

The data generated in this study support the hypothesis that HNE plays a dual role in OA cartilage degradation. At posttranslational level, HNE promotes modification of type II collagen and MMP-13 by adducts formation. At transcriptional level, HNE inhibits type II collagen and TIMP-1 synthesis and induces MMP-13 synthesis and activity.

Support: This work was supported by FRSQ