RESUMO
Amibegron, a ß3-adrenergic receptor (B3AR) agonist, has recently been shown to provide therapeutic effects for chronic rotator cuff (RC) tears by inducing the expression of uncoupling protein 1 (UCP-1), a marker of brown fat, in fibroadipogenic progenitors (FAPs). However, it remains to be seen if these beneficial effects hold true with age and in older, more clinically relevant populations. This study seeks to understand the impacts of aging on the efficacy of amibegron to treat chronic RC tears. Young (4-month-old) and aged (33-month-old) C57BL/6 mice underwent a RC injury procedure with delayed repair (DR). Mice were equally randomized to receive amibegron or dimethyl sulfoxide (DMSO) treatments after repair. Functional ability was measured at baseline and 6-weeks after DR. Wet muscle weight and histology of injured and contralateral supraspinatus were also analyzed 6-weeks post-DR. For in vitro histology and real-time quantitative PCR experiments, FAPs were isolated from young and aged mice via fluorescence-activated cell sorting. Young and aged FAPs were treated with amibegron or DMSO either immediately after seeding (early exposure) or 8-days after seeding (late exposure). In vitro results showed that amibegron-mediated FAP UCP-1 expression decreases with age. In vivo data demonstrated that aged mice have a decreased responsiveness to amibegron and decreased propensity for intramuscular FAP UCP-1 expression. Further, delayed amibegron treatment with RC repair did not lead to improvements in muscle atrophy and functional outcomes. Our findings demonstrate that age and the timing of interventions play a critical role in FAP-targeted therapeutics for chronic injuries.
RESUMO
PURPOSE OF REVIEW: Scheuermann's kyphosis (SK) is a developmental deformity of the spine that affects up to 8% of children in the US. Although, the natural progression of SK is noted to be gradual over years, severe deformity can be associated with significant morbidity. Thorough clinical examination and interpretation of relevant imaging help differentiate and confirm this diagnosis. Treatment includes both operative and nonoperative approaches. The purpose of this article is to provide an updated overview of the current theories of its pathogenesis, as well as the principles of diagnosis and treatment of SK. RECENT FINDINGS: Although a definitive, unified theory continues to be elusive, numerous reports in the past decade provide insight into the pathophysiology of SK. These include alterations in mechanical stress and/or hormonal disturbances. Candidate genes have also been identified to be linked to the inheritance of SK. Updates to nonoperative treatment include the effectiveness of dedicated exercise programs, as well as the types and duration of orthotic treatment. Advances in surgical technique can be observed with a trend toward a posterior-only approach, with supporting evidence for careful evaluation of both the sagittal and coronal planes to determine fusion levels in order to avoid postoperative junctional pathologies. SK is an important cause of structural or rigid kyphosis. It can lead to significant morbidity in severe cases. Treatment is based on curve magnitude and symptoms. Nonoperative treatment consists of physical therapy in symptomatic patients, and bracing can be added for skeletally mature patients. Operative management can be considered in patients with large, progressive, and symptomatic deformity. Future studies can benefit from a focused investigation into patient-reported outcomes after undergoing appropriate treatment.
