Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs) could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA) polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1) in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.

Rumination is a cognitive process involving repetitive thoughts about negative experiences and emotions and is associated with psychopathology. Rumination has been implicated in mood and anxiety disorders, and there is a growing body of research on rumination in relation to eating disorder (ED) psychopathology. The current meta-analytic review focused on the literature addressing rumination and ED psychopathology. A comprehensive search process identified 38 studies, which primarily used cross-sectional designs with non-clinical samples. Results demonstrated that rumination was concurrently (r = 0.33) and prospectively (r = 0.22-0.23) associated with ED psychopathology, and that groups with ED psychopathology evidenced higher levels of rumination compared to non-ED control groups (g = 0.95), though no significant differences in rumination were observed when comparing anorexia nervosa to bulimia nervosa groups (g = 0.09). In addition, a narrative review of five experimental studies suggested that rumination in response to ED-related stimuli was related to increased negative affect and negative body-related cognitions across clinical and non-clinical samples. The type of rumination and sample population emerged as moderators of effect sizes, such that larger effects were observed among samples using ED-specific measures of rumination and heterogeneous samples compared to only non-clinical samples. Taken together, this literature demonstrates that rumination is a salient process in ED psychopathology, though the literature is characterized by methodological limitations and the need for more fully elaborated theories on the role of rumination in EDs. Findings are discussed in the context of existing models of rumination and ED psychopathology, with suggestions for future research in this area.

While these reviews have generally suggested varying patterns of neurocognitive deficits across EDs, there remain critical limitations regarding the methodological quality of these studies (e.g., the lack of prospective designs, consideration of confounding influences, or examination of interrelationships between neurocognitive domains and relationships between neurocognition and other relevant behavioral constructs). Specifically, we outline 10 key areas that are imperative to address in future research in this area in order to move our field forward.

Findings suggest that symptoms related to shape and weight concerns and guilt are central ED symptoms, while physical symptoms, self-esteem, and feeling overwhelmed are links that may underlie comorbidities in EDs. Results provided some support for the validity of network approaches, in that admission networks conveyed prognostic information. However, the lack of correspondence between symptom reduction and change in network strength indicates that future research is needed to examine network dynamics in the context of intervention and relapse prevention.