4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts.

Short stature is a major skeletal phenotype in osteogenesis imperfecta (OI), a genetic disorder mainly caused by mutations in genes encoding type I collagen. However, the underlying mechanism is poorly understood, and no effective treatment is available. In OI mice that carry a G610C mutation in COL1A2, we previously found that mature hypertrophic chondrocytes (HCs) are exposed to cell stress due to accumulation of misfolded mutant type I procollagen in the endoplasmic reticulum (ER).

The extended chondrocyte lineage: implications for skeletal homeostasis and disorders.

Endochondral bone formation relies on a finely controlled sequence of chondrocyte proliferation, maturation and hypertrophy that establishes the growth plate which, combined with the deposition of bone upon the cartilage template, mediates longitudinal skeletal growth. Recent lineage studies support a chondrocyte-osteoblast differentiation continuum and the presence of skeletal stem cells within cartilage. The biological significance of the lineage extension and the mechanisms controlling the process are unclear.

Acquisition of multipotent and migratory neural crest cells in vertebrate evolution.

The emergence of multipotent and migratory neural crest (NC) cells defines a key evolutionary transition from invertebrates to vertebrates. Studies in vertebrates have identified a complex gene regulatory network that governs sequential stages of NC ontogeny. Comparative analysis has revealed extensive conservation of the overall architecture of the NC gene regulatory network between jawless and jawed vertebrates.

Mutations in Hnrnpa1 cause congenital heart defects.

Incomplete penetrance of congenital heart defects (CHDs) was observed in a mouse model. We hypothesized that the contribution of a major genetic locus modulates the manifestation of the CHDs. After genome-wide linkage mapping, fine mapping, and high-throughput targeted sequencing, a recessive frameshift mutation of the heterogeneous nuclear ribonucleoprotein A1 (Hnrnpa1) gene was confirmed (Hnrnpa1ct).

Depletion of annexin A5, annexin A6, and collagen X causes no gross changes in matrix vesicle-mediated mineralization, but lack of collagen X affects hematopoiesis and the Th1/Th2 response.

Numerous biochemical studies have pointed to an essential role of annexin A5 (AnxA5), annexin A6 (AnxA6), and collagen X in matrix vesicle-mediated biomineralization during endochondral ossification and in osteoarthritis. By binding to the extracellular matrix protein collagen X and matrix vesicles, annexins were proposed to anchor matrix vesicles in the extracellular space of hypertrophic chondrocytes to initiate the calcification of cartilage. However, mineralization appears to be normal in mice lacking AnxA5 and AnxA6, whereas collagen X-deficient mice show only subtle alterations in the growth plate organization.