Peracetylated N-Acetylmannosamine, a Synthetic Sugar Molecule, Efficiently Rescues Muscle Phenotype and Biochemical Defects in Mouse Model of Sialic Acid-deficient Myopathy

Abstract

Background: Distal myopathy with rimmed vacuoles/hereditary inclusion body myopathy (DMRV)/hIBM is a sialic aciddeficient myopathy. Results: Tissue sialylation in DMRV/hIBM mice is efficiently increased by Ac 4 ManNAc, a synthetic compound. Conclusion: Ac 4 ManNAc rescued muscle phenotype in DMRV/hIBM more efficiently than natural compounds. Significance: Application of this compound includes its potential use in therapy and in understanding the molecular basis of sialic acid deficiency in disease.

Short-Chain Fatty Acid-Modified Hexosamine for Tissue-Engineering Osteoarthritic Cartilage

“…Specifically, 3,4,6-O-Bu 3 GlcNAc induced an increase in sGAG accumulation starting at 25 mM and continued through 100 mM 3,4,6-O-Bu 3 GlcNAc exposure in IL-1b-stimulated chondrocytes (Fig. 3C).…”

“…14 Tissue was minced into small pieces (*1 mm 3 ) and digested for 18 h at 37°C in a high-glucose Dulbecco's modified Eagles' medium (DMEM; Gibco, Grand Island, NY) containing 2 mg/mL type II collagenase (Worthington Biochemical Corp., Lakewood, NJ), 5% fetal bovine serum (FBS), 100 U/ mL penicillin, and 100 mg/mL streptomycin on an orbital shaker. The cell suspension was passed through a 70-mm cell strainer and cell centrifuged to form a pellet.…”

“…After 24 h, the medium was changed to a medium supplemented with or without 50 mM 3,4,6-OBu 3 GlcNAc with the respective IL-1b concentration and incubated for an additional 4 or 24 h.…”

“…To further investigate the impact of 3,4,6-O-Bu 3 GlcNAc on ECM accumulation, the total collagen content of the cellladen hydrogels was quantified. 3,4,6-O-Bu 3 GlcNAc induced a significant increase in total collagen accumulation at 50 and 100 mM 3,4,6-O-Bu 3 GlcNAc exposure in IL-1b-stimulated chondrocytes (Fig.…”

“…It is well known that diseased chondrocytes synthesize less ECM than normal chondrocytes contributing to the net loss of ECM. 2,3 Matrix metalloproteinase-2, -9, and -13 (MMP2, MMP9, and MMP13), a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4 and ADAMTS-5), inducible nitric oxide synthase (iNOS), and both cyclooxygenases and prostaglandin E synthases (PGES) are increased in the OA joint facilitating ECM degradation or inhibit the synthesis of a new ECM. 4 Inflammation is believed to play a key role in this matrix imbalance 5 with the nuclear factor kB (NFkB) playing a pivotal role in transcriptionally regulating the expression of MMPs, proinflammatory cytokines, and transcription factors and their regulators.…”