MSCs isolated from bone marrow have been the best characterised approach for osteogenic differentiation. Their use with synthetic scaffolds such as hydroxyapatite and tricalcium phosphate has produced promising clinical results. MSCs derived from adipose tissue, muscle or human umbilical cord cells combined with various scaffolds are an attractive option. Further in vivo and clinical investigation of their potential is required. Pluripotent ESCs have a theoretical advantage over MSCs; however, purification, cell-specific differentiation, effective delivery vehicles-scaffolds and teratogenesis control are still under in vitro and in vivo evaluation.
Clinical applications for MSCs have shown promise in a number of inflammatory and autoimmune disorders. Future work is likely to further reveal the immunosuppressive characteristics of MSCs, their role in the pathophysiology of joint diseases and provide the basis for new avenues for treatment.
We demonstrate robust evidence that MSCs have the potential to regenerate articular cartilage. We also identify the complexity of designing a suitable preclinical model and the challenges in considering its clinical application such as type of MSC, scaffold, culture construct and the method by which growth factors are delivered. Of great interest is further characterization of the factors that may prevent MSC-derived chondrocytes to undergo premature hypertrophy and to understand what enables the terminal developmental pathway for permanent hyaline cartilage regeneration. Despite this, there is an abundance of evidence suggesting that MSCs are a desirable cell source and will have significant impact in tissue engineering of cartilage in the future.
Eating disorders are associated with a multitude of metabolic abnormalities which are known to adversely affect bone metabolism and structure. We aimed to comprehensively review the literature on the effects of eating disorders, particularly anorexia nervosa (AN), on bone metabolism, bone mineral density (BMD), and fracture incidence. Furthermore, we aimed to highlight the risk factors and potential management strategies for patients with eating disorders and low BMD. We searched the MEDLINE/OVID (1950-July 2011) and EMBASE (1980-July 2011) databases, focussing on in vitro and in vivo studies of the effects of eating disorders on bone metabolism, bone mineral density, and fracture incidence. Low levels of estrogen, testosterone, dehydroepiandrosterone, insulin-like growth factor-1 (IGF-1), and leptin, and high levels of cortisol, ghrelin, and peptide YY (PYY) are thought to contribute to the 'uncoupling' of bone turnover in patients with active AN, leading to increased bone resorption in comparison to bone formation. Over time, this results in a high prevalence and profound degree of site-specific BMD loss in women with AN, thereby increasing fracture risk. Weight recovery and increasing BMI positively correlate with levels of IGF-1 and leptin, normalisation in the levels of cortisol, as well as markers of bone formation and resorption in both adolescent and adult patients with AN. The only treatments which have shown promise in reversing the BMD loss associated with AN include: physiologic dose transdermal and oral estrogen, recombinant human IGF-1 alone or in combination with the oral contraceptive pill, and bisphosphonate therapy.
This observational study aimed to examine the clinimetric properties of the Greek for Greece translation of the Western Ontario and McMaster Osteoarthritis Index (WOMAC(®)). One hundred and twenty-three patients with knee osteoarthritis (mean age 69.5 years) participated in the study. An extensive reliability study was carried out to assess WOMAC's internal consistency and repeatability (8-day interval). In addition, we examined the construct (convergent, nomological and known-groups) and criterion-related (concurrent and predictive) validity of the index against both self-report [SF-36 and combined visual analog/faces pain scale-revised (VAS/FPS-R)] and physical performance measures [timed up and go test (TUG)]. The internal consistency of the WOMAC subscales ranged from high (0.804) to excellent (0.956). Intra-class correlation coefficients for test-retest reliability were excellent, ranging from 0.91 to 0.95. Partial correlation analysis, adjusted for age and use of an assistive device, showed that WOMAC scores were significantly associated with all validation criteria, presenting fair to strong (-0.33 to -0.86) correlation coefficients. WOMAC-function was strongly associated with SF36-function (-0.86) and TUG (0.71), WOMAC-pain to VAS/FPS-R (0.71) and SF36-pain (-0.67). Of all WOMAC outcomes, stiffness subscale had the lowest, though still significant, correlations with all validation criteria. Multiple linear regression analyses indicated that WOMAC-function was a significant factor for TUG, WOMAC-pain for VAS/FPS-R and both for SF36-function and SF36-pain. The WOMAC LK3.1 Greek for Greece Index is a reliable and valid assessment tool for the evaluation of individuals with knee osteoarthritis, showing excellent reliability and significant validity properties.
The data support the further investigation of this agent for the promotion of fracture healing. We aim to review the current literature and present an update on the use of this agent to promote bone formation and healing.
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