New gene associations in osteoarthritis: what do they provide, and where are we going?

PURPOSE OF REVIEW: Osteoarthritis is a serious medical, social and economic problem affecting populations worldwide. Identifying susceptibility genes for osteoarthritis is a critical step in tackling this disease. The association study is today's most powerful tool for finding such genes, and the osteoarthritis research community has enjoyed initial success through the identification of several promising candidates. This review summarizes recent advances and emerging challenges in osteoarthritis association studies. RECENT FINDINGS: Replication studies have confirmed association of functional sequence variations in the secreted frizzled-related protein 3 (FRZB) and asporin (ASPN) genes with osteoarthritis. These studies have also prompted discussion of population-specific differences in reported associations. Association of several other promising genes with osteoarthritis, including LRCH1, RHOB, TXNDC3 and GDF5, await replication. The Human Genome Project and the International HapMap Project have established an infrastructure to support genome-wide association studies. Large-scale case-control association scans are underway, and genome-wide association scans are also beginning. SUMMARY: Due to initial success in confirming several susceptibility genes and the advent of the post-genome sequence era, this area of osteoarthritis study is expanding quickly. To overcome current challenges and to move on to the next stage, however, international collaboration based on a common platform is essential.     

Alternative therapies: what role do they have in the management of lupus?

Systemic lupus erythematosus (SLE) is an autoimmune disease with higher morbidity and mortality among ethnic Chinese patients than Whites. Corticosteroid and other immunosuppressive drugs, including cyclophosphamide, azathioprine, and hydroxychloroquine are traditional therapies for this disease. Since the year 2000, mycophenolate mofetil and rituximab have been widely used in refractory SLE or severe lupus nephritis. Because the high disease activity remains, even after active therapy, and serious side effects from Western medicines may develop, more than 40% of SLE patients in Western countries are pursuing complementary and alternative therapies (CATs). CAT remedies are multiplex, and include herbal medicines, diets and vitamins, acupuncture, chiropractice, folk medicine, massage, spiritual healing, etc. Many herbal formulas have been used but in general their efficacy in treating lupus is doubted because of the lack of strong evidence. Tripterygium (T2) has demonstrated good efficacy in rheumatoid arthritis (RA) and SLE, but widespread use is limited due to the side effects. Through randomized clinical trials, we hope in the future that some Chinese medicines may be found helpful as CATs for SLE.     

The pathobiological mechanisms of emphysema models: what do they have in common?

Emphysema results from a multi-step, complex, process of lung destruction. This review aims at organizing the available information concerning the animal models of emphysema as to which step of the pathogenesis they address. The experimental models have been classified as to whether they are based on: (a) pharmacological, (b) environmental, or (c) genetic manipulations to induce emphysema and whether they are: (a) triggers or initiators of emphysema, (b) modifiers of lung predisposition to further damage by trigger factors, or (c) mediators of lung tissue destruction.     

Chlamydial nucleic acids in synovium in osteoarthritis: what are the implications?

OBJECTIVE: To study whether there is evidence of bacterial DNA in some osteoarthritic (OA) joint tissues, and the clinical implications of finding bacterial DNA in this relatively noninflammatory disease. METHODS: Polymerase chain reaction (PCR) was used to detect DNA of Chlamydia trachomatis, Chlamydia pneumoniae, and other bacteria using panbacterial primers in synovial membranes and other articular tissues of 32 consecutive patients undergoing surgery for hip and knee OA. Patients were interviewed and examined postoperatively. Operative reports were reviewed and followup examinations were accomplished on all patients. RESULTS: Nine of 32 patients with OA (28.1%) had evidence for bacterial DNA in joint tissues with at least one set of primers for Chlamydia: 7 for C. trachomatis (21.9%), 2 for C. pneumoniae (6.2%). Five of 32 (15.6%) patients had postoperative complications; 3 of these were in patients who showed amplified DNA of C. trachomatis in joints and one in a patient in whom we detected Escherichia coli. CONCLUSION: C. trachomatis and C. pneumoniae nucleic acids can be present in joints in some cases of apparently classical OA. Whether chlamydial or other difficult to culture bacterial presence is associated with complications is suggested, but remains to be determined. Simple presence of C. trachomatis by PCR does not define a clinical syndrome or disease course.