Master Series Black Silicone Bone Gag

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For intermediate users, there are a bit more options. When you are comfortable wearing a ball gag you can start using something like a lip gag or ring gag, like these for example: Gori F, Schipani E, Demay MB (2001) Fibromodulin is expressed by both chondrocytes and osteoblasts during fetal bone development. J Cell Biochem 82: 46–57. pmid:11400162

Chondroitin sulfate is historically known for its clinical use as a disease-modifying osteoarthritis drug (DMOAD). Clinical trials have documented its potential for symptomatic pain relief as well as the structure-modifying effect in osteoarthritis (OA) based on radiographic joint findings. [12] There are multiple mechanisms by which chondroitin sulfate is responsible for these clinical effects. The pain-relieving properties of chondroitin sulfate in OA relate to its anti-inflammatory properties that cause attenuation of the nuclear factor-kappa-B (NF-kappa-B) pathway that is overactive in OA. [13] Schmidt-Schultz TH, Schultz M (2004) Bone protects proteins over thousands of years: extraction, analysis, and interpretation of extracellular matrix proteins in archeological skeletal remains. Am J Phys Anthropol 123: 30–39. pmid:14669234 The first time I used this gag changed everything for me. My boyfriend and I have a pretty distinct relationship in which he is the dominant one and I am the submissive little slut that does his bidding. Rucci N, Rufo A, Alamanou M, Capulli M, Del Fattore A, et al. (2009) The glycosaminoglycan-binding domain of PRELP acts as a cell type-specific NF-kappaB inhibitor that impairs osteoclastogenesis. J Cell Biol 187: 669–683. pmid:19951916Heparan sulfate is one of the most well-studied GAGs due to its many roles and potential use as a pharmacological target for cancer treatment. Noteworthy functions of heparan sulfate include extracellular matrix (ECM) organization and modulation of cellular growth factor signaling by acting as a bridge between receptors and ligands. In the extracellular matrix, heparan sulfate interacts with many compounds including collagen, laminin, and fibronectin to promote cell to cell and cell to extracellular matrix adhesion. In the setting of malignancy such as melanoma, degradation of heparan sulfate in the extracellular matrix by the action of the enzyme heparanase leads to migration of malignant cells and metastasis. This mechanism makes heparanase and heparan sulfate viable pharmacological targets for the prevention of cancer metastasis. [1] Iozzo RV (1997) The family of the small leucine-rich proteoglycans: key regulators of matrix assembly and cellular growth. Crit Rev Biochem Mol Biol 32: 141–174. pmid:9145286 Nikitovic D, Aggelidakis J, Young MF, Iozzo RV, Karamanos NK, et al. (2012) The biology of small leucine-rich proteoglycans in bone pathophysiology. J Biol Chem 287: 33926–33933. pmid:22879588

Embery G, Hall R, Waddington R, Septier D, Goldberg M (2001) Proteoglycans in dentinogenesis. Crit Rev Oral Biol Med 12: 331–349. pmid:11603505 Catini C, Gheri G (1990) The GAGs of the bone: a study on human calva. Arch Ital Anat Embriol 95: 237–240. pmid:2129318 Keene DR, San Antonio JD, Mayne R, McQuillan DJ, Sarris G, et al. (2000) Decorin binds near the C terminus of type I collagen. J Biol Chem 275: 21801–21804. pmid:10823816 Neame PJ, Kay CJ, McQuillan DJ, Beales MP, Hassell JR (2000) Independent modulation of collagen fibrillogenesis by decorin and lumican. Cell Mol Life Sci 57: 859–863. pmid:10892350Heparan sulfate also plays a key role in cellular growth factor signaling. One example of this role involves the interaction of heparan sulfate with fibroblast growth factor (FGF) and fibroblast growth factor receptor (FGFR). Heparan sulfate facilitates the formation of FGF-FGFR complexes, resulting in a signaling cascade that leads to cellular proliferation. The degree of sulfation of heparan sulfate influences the formation of these complexes. For example, the proliferation of melanoma cells gets stimulated by the action of highly sulfated heparan sulfate on FGF. [1] Hildebrand A, Romaris M, Rasmussen LM, Heinegard D, Twardzik DR, et al. (1994) Interaction of the small interstitial proteoglycans biglycan, decorin and fibromodulin with transforming growth factor beta. Biochem J 302 (Pt 2): 527–534. pmid:8093006 Kjellen L, Lindahl U (1991) Proteoglycans: structures and interactions. Annu Rev Biochem 60: 443–475. pmid:1883201 Silva M, Dietrich CP, Nader HB (1976) On the structure of heparitin sulfates. Analyses of the products formed from heparitin sulfates by two heparitinases and a heparinase from Flavobacterium heparinum. Biochim Biophys Acta 437: 129–141. pmid:132967

HPLC analysis identified the CS population extracted from the archaeological human bone samples as over 95% C6S and less than 5% C4S. Previous research has reported a CS population of predominantly C6S in a mixture of human dentine and cementum from fresh adult teeth, with smaller amounts of C4S [ 51]. Our findings differ to those observed for human femoral compact bone in autopsy cases and human alveolar bone samples obtained from oral surgical procedures, which identified only C4S as the extracted CS [ 52, 53].Igwe JC, Gao Q, Kizivat T, Kao WW, Kalajzic I (2011) Keratocan is expressed by osteoblasts and can modulate osteogenic differentiation. Connect Tissue Res 52: 401–407. pmid:21405980

Passerotti CC, Bonfim A, Martins JR, Dall'Oglio MF, Sampaio LO, et al. (2006) Urinary hyaluronan as a marker for the presence of residual transitional cell carcinoma of the urinary bladder. Eur Urol 49: 71–75. pmid:16310928

For advanced users, there is a sea of options. From beginner to expert ones, you will have options for any play you want. Some examples of advanced ball gags are: Vejlens L (1971) Glycosaminoglycans of human bone tissue. I. Pattern of compact bone in relation to age. Calcif Tissue Res 7: 175–190. pmid:4254366 Scott JE (1996) Proteodermatan and proteokeratan sulfate (decorin, lumican/fibromodulin) proteins are horseshoe shaped. Implications for their interactions with collagen. Biochemistry 35: 8795–8799. pmid:8688414 Boskey AL, Spevak L, Doty SB, Rosenberg L (1997) Effects of bone CS-proteoglycans, DS-decorin, and DS-biglycan on hydroxyapatite formation in a gelatin gel. Calcif Tissue Int 61: 298–305. pmid:9312200