Small leucine-rich proteoglycans in physiological and biomechanical function of bone

Proteoglycans (PGs) contain long unbranched glycosaminoglycan (GAG) chains attached to core proteins. In the bone extracellular matrix, PGs represent a class of non-collagenous proteins, and have high affinity to minerals and collagen. Considering the highly negatively charged character of GAGs and their interfibrillar positioning interconnecting with collagen fibrils, PGs and GAGs play pivotal roles in maintaining hydrostatic and osmotic pressure in the matrix. In this review, we will discuss the role of PGs, especially the small leucine-rich proteoglycans, in regulating the bioactivity of multiple cytokines and growth factors, and the bone turnover process. In addition, we focus on the coupling effects of PGs and GAGs in the hydration status of bone extracellular matrix, thus modulating bone biomechanical properties under physiological and pathological conditions.