Metabolics of Chondrogenesis

Metabolomic Analysis of Differential Changes in Metabolites during ATP Oscillations in Chondrogenesis.

"Prechondrogenic condensation is a critical step for skeletal pattern formation. ATP oscillations play an essential role in prechondrogenic condensation{Maybe LSJL can mimic these ATP oscillations to induce prechondrogenic condensation}. 93 cationic and 109 anionic compounds derived from known metabolic pathways [are involved in chondrogenesis]. 15 cationic and 18 anionic compounds revealed significant change between peak and trough of ATP oscillations. Glycolysis, mitochondrial respiration and uronic acid pathway oscillate in phase with ATP oscillations, while PPRP and nucleotides synthesis pathways oscillate in antiphase with ATP oscillations. ATP-producing glycolysis and mitochondrial respiration oscillate in antiphase with the ATP-consuming PPRP/nucleotide synthesis pathway during chondrogenesis. "

"extracellular ATP and cAMP/PKA signaling mediate ATP oscillations during chondrogenesis"

"ATP oscillations were generated 2–4 d after chondrogenic induction"

"Besides ATP, 3 cationic compounds such as O-acetylcarnitine, phosphorylcholine, and tyramine and 11 anionic compounds such as fructose 1,6-bisphosphate, malate, fumaric acid, 2-oxoglutarate,cis-aconitic acid, 1,3-bisphosphoglycerate, 2-phosphoglycerate, 3-phosphoglycerate, NADH,UDP-glucuronic acid, and glucuronic acid were significantly increased at the peak of PACTIN-PxRe oscillations"<-These compounds likely oscillate along with ATP. 

Carnitine related genes upregulated by LSJL:
Down:
Crat
Cpt1b

Choline genes Up:
 Lrat
Chrna4
Chrna3

Down:
Cdc2l5
Pafah1b2
Gnb1
Chrna10
Aytl1

Malate genes Up:
Me3

NADH genes Down:
Ndufb8

"glycolysis and TCA cycle oscillate during ATP oscillations."

"glycolytic and mitochondrial oscillations are interdependent on each other."

"NADH oscillates in phase with ATP oscillations."

"oscillatory activity of carnitine O-acetyltransferase may mediate prechondrogenic condensation by modulating cellular proliferation."

"uridine diphosphate (UDP)-glucuronic acid and glucuronic acid were significantly increased in the peak of ATP oscillations. UDP-glucuronic acid is the active form of glucuronic acid for the incorporation of glucuronic acid into chondroitin sulphate. UDP-glucuronic acid is produced from glucose via uronic acid pathway: glucose 6-phosphate is isomerized to glucose 1-phosphate, which then reacts with uridine triphosphate (UTP) to form UDP glucose in a reaction catalyzed by UDP-glucose pyrophosphorylase, and subsequently UDP glucose is oxidized by NAD-dependent UDP-glucose dehydrogenase to yield UDP-glucuronic acid"

"ATP oscillations lead to prechondrogenic condensation by inducing oscillatory secretion of adhesion molecules and ECM involved in cell-cell adhesion"

"Ca2+ influx was shown to mediate ATP oscillations in chondrogenesis"

"12 cationic compounds such as diethanolamine, glycine, guanine, cyclohexylamine, glutamine, aspartic acid, 2-aminoisobutyric acid, methionine sulfoxide, proline, threonine, asparagine, and hydroxyproline and 6 anionic compounds such as phosphoribosylpyrophosphate (PPRP), ADP, dCTP, UDP, GMP, and cGMP were significantly increased in the trough of PACTIN-PxRe oscillations"

Genes in LSJL involved in Glycolysis according to Gene Ontology:
The chemical reactions and pathways resulting in the breakdown of a monosaccharide (generally glucose) into pyruvate, with the concomitant production of a small amount of ATP. Glycolysis begins with phosphorylation of a monosaccharide (generally glucose) on the sixth carbon by a hexokinase, and ends with the production of pyruvate. Pyruvate may be converted to ethanol, lactate, or other small molecules, or fed into the TCA cycle.

Down:
HK1
Eno1
Pdha1
Aldob

Genes in LSJL involved in Metabolism according to Gene Ontology:
The chemical reactions and pathways, including anabolism and catabolism, by which living organisms transform chemical substances. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation.

Up:
Ch25h
4933405O20Rik
Sulf1
Slc27a3
Lama4
Agbl2
Gfpt2
Cav3

Down:
Acsl6
Wwox
Aspa
Oxct1
Pecr
Tecta
Atp2a2
Fah
Pdhx
Acsl5
Aldh1a3
Prim2
Idh3g
Ugp2
Partial Gstm6 protein
Chi3l3
Slc6a13
Pdha1
Nat2
Cdyl
Nanp
Pah
Hsdl1