Marija Mazor

Mesenchymal stem-cell potential in cartilage repair: an update.

Articular cartilage damage and subsequent degeneration are a frequent occurrence in synovial joints. Treatment of these lesions is a challenge because this tissue is incapable of quality repair and/or regeneration to its native state. Non‐operative treatments endeavour to control symptoms and include anti‐inflammatory medications, viscosupplementation, bracing, orthotics and activity modification. Classical surgical techniques for articular cartilage lesions are frequently insufficient in restoring normal anatomy and function and in many cases, it has not been possible to achieve the desired results. Consequently, researchers and clinicians are focusing on alternative methods for cartilage preservation and repair. Recently, cell‐based therapy has become a key focus of tissue engineering research to achieve functional replacement of articular cartilage. The present manuscript is a brief review of stem cells and their potential in the treatment of early OA (i.e. articular cartilage pathology) and recent progress in the field.

Changes in prevalence of calcaneal spurs in men & women: a random population from a trauma clinic

BackgroundThis study reports the changing prevalence of ankle (Achilles and plantar) spurs with age, in order to comment on their significance to rheumatologists.Methods1080 lateral ankle radiographs from each of 9 (50 men and 50 women) age cohorts from 2 to 96 years old of patients attending a trauma clinic were examined and spurs classified as small or large.ResultsThe prevalence of both Achilles and plantar spurs in relation to the age categories and sex was variable. Overall, there was 38% of the population who had a spur (Achilles or plantar) and only third (11%) with spurs at both sites (Achilles and plantar). Large spurs were more prevalent in older individuals (40 to 79 years). There were no large plantar spurs in individuals <40 years of age and only 2% for the Achilles. The prevalence of spurs (Achilles and plantar) was significantly higher for woman than men in individuals <50 years of age. There was a notable moderate positive correlation (r = 0.71) between both plantar and Achilles spurs for women <30 years of age but no correlation for men (r = -0.03).ConclusionPlantar and Achilles spurs are highly prevalent in older people and the radiographic appearance of spurs differs between men and women. In individuals < 50 years of age, spur (Achilles and plantar) formation is more common in women than in men. Additionally, there was a notable moderate positive correlation between Achilles and plantar spurs for women <30 years of age.

Association between individual quadriceps muscle volume/enthesis and patello femoral joint cartilage morphology.

IntroductionThe aim of this study was to determine the association between individual quadriceps muscle volumes and the quadriceps enthesis structures and cartilage morphology at the patellofemoral joint (PFJ).MethodsWe studied 12 cadavers (age 75 ± 5 years). For both legs, individual quadriceps muscles (vastus lateralis (VL), rectus femoris (RF), vastus intermedialis (VI) and vastus medialis (VM)) were dissected and their volumes measured. Cartilage areas at the PFJ were classified using the International Cartilage Repair Society (ICRS) score. Histological sections were evaluated at the quadriceps tendon enthesis (laterally, centrally and medially). Several variables were calculated on the binary images based on two-dimensional analysis. These were apparent bone area (BA) and apparent trabecular thickness (TH). A Spearman rank test was used to determine the strength of correlation between individual quadriceps muscles volume, the structure of the quadriceps tendon enthesis and the ICRS score.ResultsThe thickness of calcified fibrocartilage tissue was significantly greater in the central part of the enthesis than both medially (P = 0.03) and laterally (P = 0.04). Uncalcified fibrocartilage was significantly thicker laterally (P = 0.04) and centrally (P = 0.02) than medially. Muscle volume was highest (P <0.05) for the VL, followed by the VI, VM and RF. There was no association between total and individual muscle volumes and ICRS or BA. However, there was a strong positive correlation (r = 0.81) between the VL/VM volume ratio and BA ratio (bone volume at the lateral part divided by bone volume at the medial part). There was a moderate positive correlation between VL/VM and ICRS (r = 0.65) and between ICRS and BA ratio (lateral/medial; r = 0.74).ConclusionsIndividual and total quadriceps volumes were not correlated with cartilage loss at the PFJ or fibrocartilage thickness. However, both VL/VM and BA ratio (lateral/medial) were positively correlated with ICRS scoring and therefore could be a tool for predicting degree of PFJ osteoarthritis severity.

Progenitor Cells from Cartilage: Grade Specific Differences in Stem Cell Marker Expression

Recent research has confirmed the presence of Mesenchymal stem cell (MSC)-like progenitors (MPC) in both normal and osteoarthritic cartilage. However, there is only limited information concerning how MPC markers are expressed with osteoarthritis (OA) progression. The purpose of this study was to compare the prevalence of various MPC markers in different OA grades. Human osteoarthritic tibial plateaus were obtained from ten patients undergoing total knee replacement. Each sample had been classified into a mild or severe group according to OARSI scoring. Tissue was taken from each specimen and mRNA expression levels of CD105, CD166, Notch 1, Sox9, Acan and Col II A1 were measured at day 0 and day 14 (2 weeks in vitro). Furthermore, MSC markers: Nucleostemin, CD90, CD73, CD166, CD105 and Notch 1 were studied by immunofluorescence. mRNA levels of MSC markers did not differ between mild and severe OA at day 0. At day 14, protein analysis showed that proliferated cells from both sources expressed all 6 MSC markers. Only cells from the mild OA subjects resulted in a significant increase of mRNA CD105 and CD166 after in vitro expansion. Moreover, cells from the mild OA subjects showed significantly higher levels of CD105, Sox9 and Acan compared with those from severe OA specimens. Results confirmed the presence of MSC markers in mild and severe OA tissue at both mRNA and protein levels. We found significant differences between cells obtained from mild compared to severe OA specimens suggests that mild OA derived cells may have a greater MSC potential.

Concise Review: Knee Cartilage Repair Techniquesusing Cellular Therapy

Articular hyaline cartilage is a tissue whose mechanical properties allow joint movements with a low coefficient of friction and a high absorption of constraints. Degradation of hyaline cartilage causes functional impairment of the joint, pain and decreased quality of life. In the case of isolated cartilage lesion of the knee, a remedy that allows histological restoration of cartilage and therefore a functional improvement for the long-term represents a therapeutic challenge. The hyaline cartilage is organized into four distinct layers. It is a non-vascularised and non-innervated tissue [1] composed of chondrocytes, which come from the undifferentiated mesenchymal stem cells, immersed in an extracellular matrix. This matrix synthesized by chondrocytes consists mainly of water, electrolytes, collagen (type II mainly, IX and XI), proteoglycans (aggrecan) and glycoproteins. Production of the extracellular matrix is a function of various parameters such as growth factors, intra-articular mechanical stress, hormones or age.

Effects of anti-sclerostin antibody and running on bone remodeling and strength

Sclerostin antibody (Scl-Ab) represents a promising therapeutic approach to treat patients with osteoporosis. Purpose: The aim of this study was to investigate the effects of Scl-Ab, running and a combination of both on bone formation. Methods: Sixty female Wistar rats, aged 8 months were randomly assigned to five groups (subcutaneous injections performed twice a week): (1) (Sham): sedentary rats + saline, (2) (OVX): ovariectomized rats + saline, (3) (OVX + E): OVX rats + saline + treadmill training (5 times/week, 1 h/day), (4) (OVX + E + S): OVX rats + treadmill training + 5 mg/kg Scl-Ab and (5) (OVX + S): OVX rats + 5 mg/kg Scl-Ab. After 14 weeks, body composition, whole body and femoral BMDs were determined by DXA and serum was collected for analysis of osteocalcin and NTX. Bone microarchitecture was analyzed using μCT and bone strength was assessed at the femur mid-shaft in 3-point bending. Results: Running exercise decreased fat mass as well as the bone resorption marker NTX relative to the non-exercised control groups, effects that were associated with a prevention of the deleterious effects of OVX on whole body and femoral BMDs. Scl-Ab increased the bone formation marker osteocalcin, which resulted in robust increases in BMD and femoral metaphyseal bone volume to levels greater than in the Sham group. OVX + S + E group did not further impact on bone mass relative to the OVX + S group. At the cortical femur diaphysis, Scl-Ab prevented the decreases in bone strength after OVX, while exercise did not affect cortical strength. Conclusion: We suggest that while running on a treadmill can prevent some bone loss through a modest antiresorptive effect, it did not contribute to the robust bone-forming effects of Scl-Ab when combined in an estrogen ablation model.