Osteosarcomas are the most frequent primary bone sarcomas, affecting mainly children, adolescents, and young adults, and with a second peak of incidence in elderly individuals. The current therapeutic management, a combined regimen of poly-chemotherapy and surgery, still remains largely insufficient, as patient survival has not improved in recent decades. Osteosarcomas are very heterogeneous tumors, both at the intra- and inter-tumor level, with no identified driver mutation. Consequently, efforts to improve treatments using targeted therapies have faced this lack of specific osteosarcoma targets. Nevertheless, these tumors are inextricably linked to their local microenvironment, composed of bone, stromal, vascular and immune cells and the osteosarcoma microenvironment is now considered to be essential and supportive for growth and dissemination. This review describes the different actors of the osteosarcoma microenvironment and gives an overview of the past, current, and future strategies of therapy targeting this complex ecosystem, with a focus on the role of extracellular vesicles and on the emergence of multi-kinase inhibitors.

The majority of anterior cruciate ligament (ACL) injuries occur during non-contact mechanisms. Knowledge of the risk factors would be relevant to help prevent athletes’ injuries. We aimed to study risk factors associated with non-contact ACL injuries in a population of athletes after ACL reconstruction. From a cohort of 307 athletes, two populations were compared according to the non-contact or contact mechanism of ACL injury. Gender, age and body mass index (BMI) were reported. Passive knee alignment (valgus and extension), knee laxity (KT-1000 test), and isokinetic knee strength were measured on the non-injured limb. The relationship between these factors and the non-contact sport mechanism was established with models using logistic regression analysis for the population and after selection of gender and cut-offs of age, BMI and knee laxity calculated from Receiver Operating Characteristics curve area and Youden index. Age, BMI, antero-posterior laxity, isokinetic knee strength, passive knee valgus and passive knee extension were associated with non-contact ACL injury. According to the multivariate model, a non-contact ACL injury was associated with non-modifiable factors, age (OR: 1.05; p = 0.001), passive knee extension (OR: 1.14; p = 0.001), and with one modifiable factor (Hamstring strength: OR: 0.27; p = 0.01). For women, only passive knee valgus was reported (OR: 1.27; p = 0.01). Age, passive knee extension and weak Hamstring strength were associated with a non-contact ACL injury. Hamstring strengthening could be proposed to prevent ACL injury in young male athletes or in case of knee laxity.

Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments.