Hematopoietic stem and progenitor cells (HSPC) reside in the bone marrow (BM) niche and serve as a reservoir for mature blood cells throughout life. Aging in the BM is characterized by low‐grade chronic inflammation that could contribute to the reduced functionality of aged HSPC. Mesenchymal stromal cells (MSC) in the BM support HSPC self‐renewal. However, changes in MSC function with age and the crosstalk between MSC and HSPC remain understudied. Here, we conducted an extensive characterization of senescence features in BM‐derived MSC from young and aged healthy donors. Aged MSC displayed an enlarged senescent‐like morphology, a delayed clonogenic potential and reduced proliferation ability when compared to younger counterparts. Of note, the observed proliferation delay was associated with increased levels of SA‐β‐galactosidase (SA‐β‐Gal) and lipofuscin in aged MSC at early passages and a modest but consistent accumulation of physical DNA damage and DNA damage response (DDR) activation. Consistent with the establishment of a senescence‐like state in aged MSC, we detected an increase in pro‐inflammatory senescence‐associated secretory phenotype (SASP) factors, both at the transcript and protein levels. Conversely, the immunomodulatory properties of aged MSC were significantly reduced. Importantly, exposure of young HSPC to factors secreted by aged MSC induced pro‐inflammatory genes in HSPC and impaired HSPC clonogenic potential in a SASP‐dependent manner. Altogether, our results reveal that BM‐derived MSC from aged healthy donors display features of senescence and that, during aging, MSC‐associated secretomes contribute to activate an inflammatory transcriptional program in HSPC that may ultimately impair their functionality.
Os trigonum impingement is a frequent cause of posterior ankle pain in ballet dancers because they need extreme plantar flexion during the execution of relevé in demipointe and en pointe positions. Clinical examination and standard and modified x-rays should be carried out to clearly identify the site and entity of the impingement. If a posterior impingement is clinically diagnosed, standard and modified magnetic resonance imaging should be also performed. From September 2005 to September 2006, we considered 186 young trainee ballet dancers. Twelve suffered from posterior ankle pain, and six of these had os trigona. We treated all the ballet dancers nonoperatively, and nine of them had good results. Conservative treatment failed in only three cases after 1-4 mos of physical and medical therapies, and, in these cases, good results were obtained through surgical excision of the accessory ossicle. Modified x-ray and magnetic resonance imaging help to determine the site and entity of the posterior impingement. If this is properly diagnosed, good results can be obtained through a nonoperative approach in a majority of cases.
Objective Femoroacetabular impingement (FAI) is a condition that has been increasingly recognized as a source of hip pain and a possible risk factor to early development of hip osteoarthritis (OA). To our knowledge, the use of HA in the treatment of femoroacetabular FAI has been investigated only by two studies, both using a high molecular weight HA. The aim of this study was to evaluate the efficacy of two weekly injections of an hexadecylamide derivative of HA (HYADD4-G, HYMOVIS, Fidia Farmaceutici) in FAI. Methods All patients received two weekly intra-articular injections of Hymovis at baseline and after 7 days. Clinical and functional assessments were performed at baseline and was repeated after 1, 3, 6 and 12 months. Functional measures included visual analogue scale (VAS) for pain, Harris Hip score (HHS), Lequesne Index (LI), Tegner activity level scale (TALS) and monthly consumption of nonsteroidal anti-inflammatory drugs (NSAIDs). Results Twenty-one hips (19 patients, 2 bilateral cases) were treated. The variables VAS, HHS as well as Lequesne improved significantly from T0 to T4 (at 12 months) with the best improvement between T0 and T1. At the same time, a reduction in NSAIDs monthly intake was registered. On the other hand, a significant improvement in Tegner scale was not observed. No adverse events were registered. Conclusion This study states that one cycle of HYADD4-G could be a safe and effective treatment in patients with FAI, showing significative results in term of pain control as well as hip functionality and quality of life up to 1 year.
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