Regenerative capacity of human pluripotent stem cell-derived articular chondrocytes in vitro.

The ideal cell source for articular cartilage repair remains elusive. Using developmentally inspired differentiation protocols, we induced human pluripotent stem cells (hPSCs) toward articular chondrocytes capable of joint cartilage repair in rodent models, which were distinct from growth plate chondrocytes, fated to be replaced by bone in vivo. Working toward clinical translation, we demonstrated controlled differentiation into chondrocytes by comprehensive gene expression analysis at each step of the differentiation.

Impact of broad regulatory regions on Gdf5 expression and function in knee development and susceptibility to osteoarthritis.

Objectives: Given the role of growth and differentiation factor 5 () in knee development and osteoarthritis risk, we sought to characterise knee defects resulting from loss of function and how its regulatory regions control knee formation and morphology.

Methods: The () mouse line, which harbours an inactivating mutation in , was used to survey how loss of function impacts knee morphology, while two transgenic reporter bacterial artificial chromosome mouse lines were used to assess the spatiotemporal activity and function of regulatory sequences in the context of clinically relevant knee anatomical features.

Results: Knees from homozygous mice () exhibit underdeveloped femoral condyles and tibial plateaus, no cruciate ligaments, and poorly developed menisci.

Dynamics and cellular localization of Bmp2, Bmp4, and Noggin transcription in the postnatal mouse skeleton.

Transcription of BMPs and their antagonists in precise spatiotemporal patterns is essential for proper skeletal development, maturation, maintenance, and repair. Nevertheless, transcriptional activity of these molecules in skeletal tissues beyond embryogenesis has not been well characterized. In this study, we used several transgenic reporter mouse lines to define the transcriptional activity of two potent BMP ligands, Bmp2 and Bmp4, and their antagonist, Noggin, in the postnatal skeleton.

An autonomous BMP2 regulatory element in mesenchymal cells.

BMP2 is a morphogen that controls mesenchymal cell differentiation and behavior. For example, BMP2 concentration controls the differentiation of mesenchymal precursors into myocytes, adipocytes, chondrocytes, and osteoblasts. Sequences within the 3'untranslated region (UTR) of the Bmp2 mRNA mediate a post-transcriptional block of protein synthesis.