Advertisement for orthosearch.org.uk
Results 1 - 2 of 2
Results per page:
Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 70 - 70
2 Jan 2024
Ely E Collins K Lenz K Paradi S Liedtke W Chen Y Guilak F
Full Access

Osteoarthritis (OA) is the leading cause of pain and disability worldwide and is characterized by the degenerative changes of articular cartilage. Joint loading is required for cartilage maintenance; however, hyper-physiologic loading is a risk factor for OA. Mechanosensitive ion channels Piezo1 and Piezo2 synergistically transduce hyper-physiologic compression of chondrocytes, leading to chondrocyte death and onset of OA. This injury response is inhibited by Piezo channel loss of function, however the mechanistic role of Piezo channels in vivo is unknown. We examined the hypothesis that deletion of Piezo in chondrocytes will protect mice from joint damage and pain-related behaviors following a surgical destabilization of the medial meniscus (DMM), investigating a key mechanistic and mechanobiological role of these channels in the pathogenesis of OA.

Aggrecan-Cre Piezo1 and Piezo1/2 knockout mice ((Agc)1-CREERT2;Piezo1fl/flPiezo2fl/fl) were generated and given a 5-day Tamoxifen regimen at 12-weeks of age (n=6–12/group/sex). Cre-negative mice served as controls. At 16-weeks, mice received DMM surgery on the left knee. 12-weeks following DMM prior to sacrifice, activity and hyperalgesia were measured using spontaneous running wheels and a small animal algometer. Structural changes in bone, cartilage, and synovium were characterized using microCT, histology, and Modified Mankin Score criteria.

Knockout of Piezo1/2 channels was chondroprotective in both sexes following DMM surgery as demonstrated by reduced Modified Mankin Score compared to control animals. Piezo1 KO was chondroprotective in only female mice, indicating a sexually dimorphic response. Piezo1 and Piezo1/2 KO was protective against pain in male mice, while females displayed no differences compared to controls. No changes were observed in bone morphology.

Chondrocyte-specific Piezo1/2 knockout protects the knee joint from structural damage, hyperalgesia and functional deficits in a surgical model of PTOA in male and female mice, illustrating the importance of Piezo channels in response to injury in vivo. Future work aims to interrogate potential sexually dimorphic responses to cartilage damage and investigating Piezo2 KO mice.


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_10 | Pages 5 - 5
1 Jun 2023
Church D Pawson J Hilton C Fletcher J Wood R Brien J Vris A Iliadis A Collins K Lloyd J
Full Access

Introduction

External fixators are common surgical orthopaedic treatments for the management of complex fractures and in particular, the use of circular frame fixation within patients requiring limb reconstruction. It is well known that common complications relating to muscle length and patient function without rehabilitation can occur. Despite this there remains a lack of high-quality clinical trials in this area investigating the role of physiotherapy or rehabilitation in the management of these patients. We aim to complete a systematic review of rehabilitation techniques for patients undergoing external fixator treatment for Limb Reconstruction of the lower limb.

Materials & Methods

A comprehensive search of AMED, CINAHL, MEDLINE and COCHRANE databases was conducted to identify relevant articles for inclusion, using a search strategy developed in collaboration with a research librarian. Inclusion criteria consisted of adults aged 18 years and over who have experienced leg trauma (open fracture, soft tissue damage), elective leg deformity corrective surgery, bone infection or fracture non-union who have been treated with the use of an external fixator for fixation. Specific exclusion criteria were patients below the age of 18 years old, patients with cancer, treatment of the injury with internal nail, patients who underwent amputation, the use of external fixators for soft tissue contracture management, editorials, comment papers, review papers, conference proceedings and non-English papers.

Titles, abstracts, and full texts were screened for suitability by pairs of reviewers according to the inclusion and exclusion criteria using Rayyan QCRI online software. Any conflicts were resolved through discussion with three independent specialist senior reviewers. Following full text screening, references lists of included articles were manually searched to ensure that all relevant studies were identified. Due to lack of evidence, forward searching was also completed for studies included in the review. Data quality was assessed using the mixed methods appraisal tool and the CERT assessment tool was utilised to look at completeness of reporting of exercise interventions.