Osteoarthritis Linked to Diabetes Characterized Sharp decreasing in Ser /Proline /PLCγ2 with Increasing PLCγ1, Where Inhibiting S6K/BTK / PLCγ2 Affect TXA2 Synthesis Cause C-lymphocytic Leukemia

Abstract

proper S6K /BTK and PLCγ2 are main regulations for thromboxane-A synthesis, and necessary for B-cell maturations and T-cells modulations and functions. The main factors that cause the Osteoarthritis “OA” and diabetes and linked between them are the deficiency of Ser amino acids and decreasing or down regulations of Ser phosphorylation signalling pathway which necessary for proper S6K productions, where normally the Ser phosphorylation signalling pathway is the basis of Ser /Thr phosphorylation signalling which normally necessary for proper Akt, S6K1 synthesis and necessary for RORs and IFNs synthesis and also necessary for running proper BTK and proper PLCγ2 productions , where S6K is main regulator for ATPase and for proper PLCγ1 and for PLCγ2 synthesis which necessary for bone growth and for increasing and modulating immune efficiency.

Osteoarthritis “OA” is characterized by a sharp expression in Gamma-Phospholipase C-1 “PLCγ1”, with decreasing “or inhibition” in PLCγ2 “PLC beta” productions. The increasing in PLCγ1 with Deficiency in Ser amino acids will lead to deficiency in Ser phosphorylation signalling (which is main basis for Ser/Thr phosphorylation signaling which has the main function of producing proper S6K) , and decreasing in synthase activity will reflect down regulations in BTK pathways and lead to inhibition in PLCγ2 producions which will reflect diabetes (inhibition in Estrogen with the production of Androgen instead of estrogen) and can reflect early Osteoarthritis”OA” prognosis dépend on the percentage of Deficiency or inhibition in basic amino acids and in basic necessary signaling pathways.

The proper S6K are so necessary for reactivating both PLCγ1&2, where phospholipase Cγ2 (PLCγ2) is activated from a variety of cell surface receptors such as SyK “S6K”. As , the B cells are promoted by the function and activities of both PLCγ1&2 , as the deficiency in Ser amino acids will reflect decreasing in Ser phosphorylation pathways and then decreasing in Estrogen synthesis, with increasing in Androgen synthesis which lead to decreasing in PLCs isoforms production and lead to pathogenic diabetes proplem. So T2DM is strongly connected with OA disease and both are having the same syndrome of causing their pathogenic problems, and any early step from any of those two or more similar diseases can lead to the other.

Pathogenic type 2 diabetes associated with progressive beta-cell impairment due to the mutations in the production of normal insulin which due to missing of Ser phosphorylation signaling during mTOR Ser/Thr phosphorylation pathways that reflect Inhibition in. The releasing of PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) which are regulating hydrophobic amino acids synthesis which can be modified by synthetase enzymes for creating the first active gamma-subunits (upon synthetase effects) that will be modified by synthase effect for Beta-subunit synthesis then for alpha subunits upon phospholipase effects respectively.

The previous of the releasing of PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) from specifically the phosphorylations of Ser pathway is so necessary steps and mechanism for normal S6K productions, necessary for IFN-Gamma and for PLCγ1 productions, and therefore necessary for normal PLCγ2 synthesis which is necessary for B-cell activities, for T-cells modulations, for modulating anti-inflammatory steps and procedures, for thromboxane-A synthesis, and for bone growth and modulation.

Inhibition in PS/T-Thymine -Kinase and PS/T-Cytosine -kinase chains (mTORC1) productions can be the main reason for inhibition the beta subunits productions that can be the reason of decreasing in the hyperpolarization and then electrical activity will lead to decreasing in the abolition of Ça+ which will lead to increasing in the dropping in blood pressure. Deficiency in conversion of glutarate to glutamate and decreasing in proline biosynthesis can affect on cartilage synthesis and bone growth due to decreasing in the activities of mitochondrial OPA1 oxidations.

It’s imp to note that Tyrosine phosphatase PTPs are important regulator of chondrogenic patterningare and are critical regulators of tyrosine phosphorylation that it’s activity depends on Tyr, Ser synthesis (hydrophobic acids) and on JAK state signaling activities. And so, the proline-rich tyrosine kinases regulate proper PLCs isoforms which compete for binding site at the very C terminus of fibroblast growth factor for osteprogenitor embryonic development, and bone formations.

Synthetase is the main regulator for PLCγ1 activities followed by synthase effects for beta-subunits (“PLCγ2”) productions which is able to “upregulate phospholipase abtivity” for alpha subunits (PLC-alpha) productions for reactivating fibroblast growth factor receptor (FGFR2) and for reactivating antigens and TLR4 productions. Where, PLCγ1 competes for a binding site at the very C terminus of FGFR2 for embryonic development and bones growth, where, PLCs isoforms are involved in multiple stages in TLR4, interferon, and in anti-inflammatory steps. And also , PLCγ1 recruit to CSF-1 is following imp stages for producing PLCγ2 which is necessary for activating anti-inflammatory where, IFN-γ activates PLC-γ2 via an upstream of tyrosine kinase.

The PLCγ1 and PLCγ2 (PLCs) are so imp in anti-inflammatory processes and can be considered as having the main roles of characterizing the activities of thromboxane and fibrin through re-modulating immune and T cells activities. Inhibitions or reduction or mutations in S6K, in BTK and in the original main normal PLCγ2 producions will cause an inherent or inhibition in CXCL12 then followed by inherent or inhibition in CXCR4 then reflect inherent or inhibition in the regulation of B-cell growth, migrations, adhesions and functions. Proline amino acids is necessary for reactivate OPA1 anabolic oxidations (started by synthetase, then synthase, then phospholipase for producing gamma “PLCγ1” , then beta “PLCγ2”, then alpha “PLC-a” subunits respectively) for cartilage synthesis which promote PLCγ2 synthesis necessary for bone growth including antigen and thromboxane-A synthesis.