R-spondins: novel matricellular regulators of the skeleton.

R-spondins are a family of four matricellular proteins produced by a variety of cell-types. Structurally, R-spondins contain a TSR1 domain that retains the tryptophan structure and a modified cysteine-rich CSVCTG region. In addition, the R-spondins contain two furin repeats implicated in canonical Wnt signaling. R-spondins positively regulate canonical Wnt signaling by reducing Wnt receptor turnover and thereby increasing beta-catenin stabilization. R-spondins are prominently expressed in the developing skeleton and contribute to limb formation, particularly of the distal digit. Additionally, results suggest that R-spondins may contribute to the maintenance of adult bone mass by regulating osteoblastogenesis and bone formation.