Physiological mechanical loading reduces inflammatory signalling in numerous cell types including articular chondrocytes however the mechanism responsible remains unclear. This study investigates the role of chondrocyte primary cilia and associated intraflagellar transport (IFT) in the mechanical regulation of interleukin-1β (IL-1β) signalling. Isolated chondrocytes and cartilage explants were subjected to cyclic mechanical loading in the presence and absence of the cytokine IL-1β. Nitric oxide (NO) and prostaglandin E2 (PGE2) release were used to monitor IL-1β signalling whilst Sulphated glycosaminoglycan (sGAG) release provided measurement of cartilage degradation. Measurements were made of HDAC6 activity and tubulin polymerisation and acetylation. Effects on primary cilia were monitored by confocal and super resolution microscopy. Involvement of IFT was analysed using ORPK cells with hypomorphic mutation of IFT88. Mechanical loading suppressed NO and PGE2 release and prevented cartilage degradation. Loading activated HDAC6 and disrupted tubulin acetylation and cilia elongation induced by IL-1β. HDAC6 inhibition with tubacin blocked the anti-inflammatory effects of loading and restored tubulin acetylation and cilia elongation. Hypomorphic mutation of IFT88 reduced IL-1β signalling and abolished the anti-inflammatory effects of loading indicating the mechanism is IFT-dependent. Loading reduced the pool of non-polymerised tubulin which was replicated by taxol which also mimicked the anti-inflammatory effects of mechanical loading and prevented cilia elongation. This study reveals that mechanical loading suppresses inflammatory signalling, partially dependent on IFT, by activation of HDAC6 and post transcriptional modulation of tubulin.

* Spinal tuberculosis (STB) is a common form of extrapulmonary tuberculosis (TB), accounting for 3.7% of TB cases in the United States. * The most common presentation is chronic back pain, for which the diagnosis of STB can be easily overlooked, leading to the development of neurological deficits and osseous deformities of the spine. * The risk of TB is increasing as a result of multidrug-resistant TB strains. * The first line of treatment is antitubercular medical therapy, with surgical intervention being indicated for decompression of neurological elements that have been unresponsive to medical therapy, the restoration of spinal stability, and the correction of deformity. * Early diagnosis and treatment improve the prognosis. * This review of the current literature on STB offers an insight into our experience on STB treatment at a western STB specialist hospital.

Agrin heals joint surfaces by recruiting joint stem cells and inducing the formation of cartilage and bone with correct architecture in mice and sheep.

Pelvic girdle pain (PGP) refers specifically to musculoskeletal pain localised to the pelvic ring and can be present at its anterior and/or posterior aspects. Causes such as trauma, infection and pregnancy have been well-established, while patients with hypermobile joints are at greater risk of developing PGP. Research exploring this association is limited and of varying quality. In the present study we report on the incidence, pathophysiology, diagnostic and treatment modalities for PGP in patients suffering from Hypermobility Spectrum Disorder (HSD) and Hypermobility-Type Ehlers-Danlos Syndrome (hEDS). Recommendations are made for clinical practice by elaborating on screening, diagnosis and management of such patients to provide a holistic approach to their care. It appears that this cohort of patients are at greater risk particularly of mental health issues. Moreover over, they may require a multidisciplinary approach for their management. Ongoing research is still required to expand our understanding of the relationship between PGP, HSD and hEDS by appropriately diagnosing patients using the latest updated terminologies and by conducting randomised control trials to compare outcomes of interventions using standardised patient reported outcome measures.