Disentangling the detrimental effects of local from systemic adipose tissue dysfunction on articular cartilage in the knee.

OBJECTIVE: Obesity increases osteoarthritis (OA) risk due to adipose tissue dysfunction with associated metabolic syndrome and excess weight. Lipodystrophy syndromes exhibit systemic metabolic and inflammatory abnormalities similar to obesity without biomechanical overloading. Here, we used lipodystrophy mouse models to investigate the effects of systemic versus intra-articular adipose tissue dysfunction on the knee. METHODS: Intra-articular adipose tissue development was studied using reporter mice. Mice with selective lipodystrophy of intra-articular adipose tissue were generated by conditional knockout (cKO) of Bscl2 in Gdf5-lineage cells, and compared with congenital Bscl2 knockout (KO) mice with generalised lipodystrophy and associated systemic metabolic dysfunction. OA was induced by surgically destabilising the medial meniscus (DMM) and obesity by high-fat diet (HFD). Gene expression was analysed by quantitative RT-PCR and tissues were analysed histologically. RESULTS: The infrapatellar fat pad (IFP), in contrast to overlying subcutaneous adipose tissue, developed from a template established from the Gdf5-expressing joint interzone during late embryogenesis, and was populated shortly after birth by adipocytes stochastically arising from Pdgfrα+ Gdf5-lineage progenitors. While female Bscl2 KO mice with generalised lipodystrophy developed spontaneous knee cartilage damage, Bscl2 cKO mice with intra-articular lipodystrophy did not, despite synovial hyperplasia and inflammation of the residual IFP. Furthermore, male Bscl2 cKO mice showed no worse cartilage damage after DMM. However, female Bscl2 cKO mice with intra-articular lipodystrophy showed increased susceptibility to the cartilage-damaging effects of HFD-induced obesity. CONCLUSION: Our findings emphasise the prevalent role of systemic metabolic and inflammatory effects in impairing cartilage homeostasis, with a modulatory role for intra-articular adipose tissue.

Integrated Behavioral Health Prevention for Infants in Pediatric Primary Care: A Mixed-Methods Pilot Study.

OBJECTIVE: Pediatric primary care is a promising setting in which to deliver preventive behavioral health services to young children and their families. Integrated behavioral health care models typically emphasize treatment rather than prevention. This pilot study examined the efficacy of an integrated behavioral health preventive (IBH-P) intervention delivered by psychologists and focused on supporting parenting in low-income mothers of infants as part of well-child visits in the first 6 months of life. METHODS: Using a mixed-methods approach that included a pilot randomized clinical trial and post-intervention qualitative interviews, 137 mothers were randomly assigned to receive IBH-P or usual care. Self-report measures of parenting, child behavior, and stress were obtained at pre- and/or post-intervention. Direct observation of mother-infant interactions was conducted at post-intervention. RESULTS: No differences between groups were found on maternal attunement, knowledge of child development, nurturing parenting, or infant behavior. A secondary analysis on a subsample with no prior exposure to IBH-P with older siblings found that mothers in IBH-P reported increased self-efficacy relative to controls. In the qualitative interviews, mothers stated that they valued IBH-P, learning about their baby, liked the integration in primary care, and felt respected and comfortable with their provider. CONCLUSIONS: Findings are discussed in terms of the next steps in refining IBH-P approaches to prevention in primary care.