Extracellular matrix glycoproteins and proteoglycans bind a variety of growth factors and cytokines thereby regulating matrix assembly as well as bone formation. However, little is known about the mechanisms by which extracellular matrix molecules modulate osteogenic stem cells and bone formation. Using mice deficient in two members of the small leucine-rich proteoglycans, biglycan and decorin, we uncovered a role for these two extracellular matrix proteoglycans in modulating bone formation from bone marrow stromal cells. Our studies showed that the absence of the critical transforming growth factor-␤ (TGF-␤)-binding proteoglycans, biglycan and decorin, prevents TGF-␤ from proper sequestration within the extracellular matrix. The excess TGF-␤ directly binds to its receptors on bone marrow stromal cells and overactivates its signaling transduction pathway. Overall, the predominant effect of the increased TGF-␤ signaling in bgn/dcn-deficient bone marrow stromal cells is a "switch in fate" from growth to apoptosis, leading to decreased numbers of osteoprogenitor cells and subsequently reduced bone formation. Thus, biglycan and decorin appear to be essential for maintaining an appropriate number of mature osteoblasts by modulating the proliferation and survival of bone marrow stromal cells. These findings underscore the importance of the micro-environment in controlling the fate of adult stem cells and reveal a novel cellular and molecular basis for the physiological and pathological control of bone mass.The extracellular matrix (ECM) 1 provides structural strength to tissues, maintains the shape of organs, and is often involved directly or indirectly in regulating cell proliferation and differentiation (1-3). ECM components modulate the bioactivities of growth factors and cytokines, such as TGF-␤, tumor necrosis factor-␣, and platelet-derived growth factor, by 1) activating them by proteolytic processing (4, 5), 2) inactivating them by sequestering and preventing binding to their respective receptors (6 -9), or 3) directly binding to cytokine receptors, such as the epidermal growth factor receptor (10, 11).Proteoglycans, which are characterized by a core protein with at least one glycosaminoglycan chain attached, commonly mediate the interactions of ECM components with growth factors and cytokines (12). Small leucine-rich proteoglycans (SLRPs) are some of the major non-collagen components of the ECM (13). The core proteins of the SLRPs consist of leucinerich repeats flanked by two cysteine-rich clusters. The size of the core proteins (ϳ40 kDa) is relatively small compared with aggrecan and versican (Ͼ200 kDa) (1, 10, 14). The SLRP superfamily currently consists of 13 known members that can be divided into 3 distinct subfamilies based on the genomic organization, structure, and similarity of their amino acid sequences (13). SLRPs are involved in skeletal growth (15-17), craniofacial structure (15), dentin formation (18), and collagen fibrillogenesis (17,19,20). However, to date, little is known about the precise mec...

Because their etiologies and pathogenesis are poorly understood, temporomandibular joint (TMJ) diseases are difficult to diagnose and manage. All current approaches to treatments of TMJ diseases are largely palliative. Definitive and rational diagnoses or treatments can only be achieved through a comprehensive understanding of the etiologies, predisposing factors, and pathogenesis of TMJ diseases. While much work remains to be done in this field, novel findings in biomedicine and developments in imaging and computer technologies are beginning to provide us with a vision of future innovations in the diagnostics and therapeutics of TMJ disorders. These advances include the identification and use of local or systemic biomarkers to diagnose disease or monitor improvements in therapy; the use of imaging technologies for earlier and more sensitive diagnostics; and the use of biomedicine, biomimetics, and imaging to design and manufacture bioengineered joints. Such advances are likely to help to customize and enhance the quality of care we provide to patients with TMJ disorders.

Most older adults have TMJ degeneration, which affects women more than men. In most older adults, the symptoms of TMD are mild and self-limiting and can usually be treated with self management.

Mechanical loading of bone may be transmitted to osteocytes and osteoblasts via shear stresses at cell surfaces generated by the flow of interstitial fluid. The stimulated production of prostaglandins, which mediates some effects of mechanical loading on bone, is dependent on inducible cyclo-oxygenase 2 (COX-2) in bone cells. We examined the fluid shear stress (FSS) induction of COX-2 gene expression in immortalized MC3T3-E1 osteoblastic cells stably transfected with ؊371/؉70 base pairs (bp) of the COX-2 5-flanking DNA (Pluc371) and in primary osteoblasts (POBs) from calvaria of mice transgenic for Pluc371. Cells were plated on collagen-coated glass slides and subjected to steady laminar FSS in a parallel plate flow chamber.