Emma L. Williams

Anti-TNF-induced lupus

The use of protein-based anti-TNF-alpha therapies such as antibodies and soluble TNF-alpha receptors is commonly associated with the induction of autoantibodies, whereas anti-TNF-induced lupus (ATIL) is rare. ATIL can occur with any of the available TNF inhibitors, but the frequency and clinical characteristics of ATIL vary between different drugs. Cutaneous, renal and cerebral involvement as well as dsDNA antibodies are more common in ATIL compared to classical drug-induced lupus (DIL), suggesting different pathogenic mechanisms of ATIL and DIL. True ATIL must be clinically differentiated from mixed CTD, SLE or overlap syndromes unmasked, but not induced, by anti-TNF-alpha treatment of unclassified polyarthritis. The pathogenesis of ATIL is still unknown. Concomitant immunosuppression can reduce autoantibody formation in ATIL, and withdrawal of anti-TNF-alpha therapy usually leads to resolution of symptoms. Steroids and/or immunosuppressive therapy may be required in severe cases.

The role of interleukin-6 in rheumatoid arthritis-associated osteoporosis.

IntroductionOsteoporosis is highly prevalent in patients with rheumatoid arthritis (RA) and is a frequent cause of fractures, disability, reduced quality of life and increased use of healthcare resources.DiscussionFactors associated with the development of osteoporosis and fractures in patients with RA include disease activity, inflammation, gender, age, low body mass and glucocorticoid exposure. Several processes contribute towards the pathology of RA-associated osteoporosis, and increased osteoclast activation and subsequent bone resorption mediated by pro-inflammatory cytokines are thought to play major roles. Given the key effects of interleukin-6 (IL-6) in both RA and osteoporosis, and its ability to modulate other inflammatory mediators, IL-6 may be an important factor specifically associated with osteoporosis in patients with RA.ConclusionThe development of agents that modulate the actions of IL-6 and those of other pro-inflammatory mediators of bone loss may provide alternative osteoporosis management strategies for patients with RA than existing general osteoporosis therapies.

Isolation and Enrichment of Stro-1 Immunoselected Mesenchymal Stem Cells from Adult Human Bone Marrow

The availability of mesenchymal stem cells (MSCs) or skeletal stem cells (SSCs) is vital to many of the tissue engineering strategies currently being developed for repairing bone and cartilage. One difficulty with using this cell population is that SSCs represent only a small fraction of the cells available from an individual patients bone marrow sample, typically less than 1 in 10,000. Therefore, methods have been devised to enrich the proportion of MSCs obtained from a bone marrow sample using hybridoma cell lines to generate antibodies to cell surface antigens specific for MSCs. Stro-1 is the most widely targeted of these cell surface antigens. The protocol described overleaf is used to isolate and enrich the Stro-1 positive fraction of cells from a bone marrow aspirate to provide a sample enriched for MSCs for use in both in vitro and in vivo studies.

Impact of inflammation on the osteoarthritic niche: implications for regenerative medicine

Osteoarthritis (OA) is the most common form of arthritis worldwide and is the sixth leading cause of disability. It costs the UK economy approximately 1% of gross national product per annum. With an aging population, the cost of chronic conditions such as OA continues to rise. Historically, treatments for OA have been limited to painkillers, physiotherapy and joint injections. When these fail, patients are referred for joint replacement surgery. With the advent of tissue engineering strategies aimed at generating new bone and cartilage for repair of osteochondral defects, there has been considerable interest in exploiting these techniques to devise new treatments for OA. To date, little consideration has been given to the OA niche and attendant inflammatory milieu for any regenerative skeletal strategy. This review highlights the importance of understanding the osteoarthritic niche in order to modify existing tissue engineering and regenerative medicine strategies for the future treatment of OA.

The osteoarthritic niche and modulation of skeletal stem cell function for regenerative medicine

Osteoarthritis (OA) is the most common cause of arthritis worldwide and represents a significant healthcare burden, particularly in the context of an ageing population. Traditionally, painkillers, injections and physiotherapy have been the mainstay of treatment, with patients being referred for joint replacement surgery (arthroplasty) when these options fail. Whilst effective in reducing pain and improving joint function, these approaches are not without potential complications. With the development of tissue‐engineering techniques over recent years there has been considerable interest in applying these strategies to provide new, innovative, alternative effective means of treating OA. This review explores the unique microenvironment present within an osteoarthritic joint, highlighting the features that comprise the osteoarthritic niche and could be modulated in the development of novel treatments for OA. Existing tissue‐engineering strategies for repairing bone and cartilage defects are discussed, with particular reference to how these might be modified, both to improve existing treatments, such as impaction bone grafting, as well as in the development of future treatments for OA. Copyright