Osteoporosis is a systemic bone disease, which leads to the deterioration of microstructure of bone tissues causing lowering of the bone mass and so consequent fracture. The imbalance of bone remodeling process leading to bone resorption and its main pathophysiological process of osteoporosis. Various types of non-skeletal factors add to fracture risk and thus, diagnostic tool for osteoporosis is the estimation of risk factors and Bone Mass Density measurement. . Bone is an active tissue thatis continuously remodeled with the help of specific bone forming cells, osteoblast and bone resorbing cells, osteoclasts. The imbalance of bone metabolism like decreasing bone resorption causes lower blood calcium level, called as hypocalcemia. Hypocalcemia is defined as blood calcium level below 8.5mg/dL or ionized blood calcium level lower than 4.6mg/dL in blood plasma. It is most common in advance stage prostate cancer patients and about approximately in 30% of cases. Osteogenesis and bone formation involve many genes, some have positive whilst some have negative impacts. Like WNTB increases osteoblast activity and RUNX2, a transcription factor involved in osteoblast differentiation and shortage of sclerostin (SOST) enhances bone formation . Signaling pathways plays a decisive role in the regulation of osteoblasts and osteoclasts that regulate the bone turn over. Osteoclast activation escort to the loss of bone, and at present therapeutic agents for osteoporosis mainly works on inhibition of bone resorption . PTHrP1-36 stimulates bone formation by reducing bone resorption. Member of TGF that’s Activin A stimulates osteoclastogenesis and also involved in the process of inhibition of bone mineralization .
Here, using different bioinformatic tools a high throughput gene expression datasets of osteoporosis vs control were studied and as the output it has revealed about 1929 were novel DEGs out of 3390. From total of 1929 novel DEGs, about 1147 DEGs were related to bone signaling only; 86 were related to osteogenesis and bone signaling both; 53 in hypocalcemia and bone signaling both; 8 DEGs were together involved in hypocalcemia, osteogenesis and bone signaling while only 4 were related to hypocalcemia and 1 in osteogenesis.
The hypocalcemia related novel DEGs forming hub nodes are mainly ITCH, CKAP4, FBXW11 and RAB37 from these the first two are upregulated and rest two are downregulated respectively.
ITCH (Itchy E3ubiquitin protein ligase) gene, a regulator of ubiquitination of T-cell receptors, and any mutation in ITCH gene can cause syndromic Multisystem Autoimmune Disease with acute liver failure.
CKAP4, Cytoskeletal-associated protein 4; also known as p63, CLIMP-63 or ERGIC-63, is a 63kDa type II transmembrane (TM) protein, residing in endoplasmic reticulum or in intermediate compartment of Golgi. CKAP4 protein is upregulated in hepatocellular carcinoma tissues and has been identified as specifically in it .
FBXW11, a F-box family members contributing to tumorigenesis and tumour development ; . A recent work revealed the role of Fbxw11 in the proliferation of lymphocytic leukemia cells and implies that it can be served as a potential molecular target for the disease treatment .
RAB37 is a small GTPase, playing important roles in several cellular processes through intracellular membrane traffic. It has been identified as a tumour suppressor and regulates exocytosis of several proteins including TIMP metallopeptidase inhibitor 1 (TIMP1) .
Similarly, the bone signaling novel DEGs forming hub nodes mainly include CHML, ATP11A, TMEM30A, YWHAE, AP1M1 and FYN from these the first three are upregulated and rest three are downregulated respectively.
CHML (Choroideremia-like) protein is essential for the prenylation modification of various Rab proteins and it exertsbiological effects on vesicle trafficking and signal transduction. CHML gene is now considered as an independent factor to evaluate the prognosis of Multiple Myeloma, and is associated with poor survival of myeloma cells .
However,ATP11A, a ubiquitously expressed gene in various tissues and deleterious effect are lethal for an organism. It plays an important role in myotube formation, while detailed cellular function of ATP11A is still remain exclusive. Mutation in this gene affects localization of Golgi and plasma membrane and Phosphatidylserine flippase activity .
TMEM30A(Transmembrane protein 30A), is a ubiquitously expressed terminally-glycosylated membrane protein . The TMEM30A phospholipid flippase complex plays role in cell migration via the formation of membrane ruffles as a result of phospholipid translocation .
YWHAE (Tyrosine 3-Monooxygenase/Tryptophan 5-Monooxygenase Activation Protein Epsilon), is a protein coding gene and its association has been found with Endometrial Stromal Sarcoma and Kidney Clear Cell Sarcoma. Mutation in this gene has now been considered a risk for Major Depressive Disorder in the Han Chinese Population .
AP1M1 (Adaptor protein-1 µ subunit-1), mediates late secretory and vascular traffic and is required for growth . Adaptor proteins (AP) are complexes predominantly as coat proteins of membrane vesicles in post-Golgi trafficking of mammalian cells. AP-1 is crucial for cell division and plant growth.
FYN, is a Src family non-receptor tyrosine kinase, which interacts with tau via SH3 domain , where tau is enriched in axons and regulates the microtubule assembly. Fly is found to be critical for neurofibrillary tangle formation and tau hyperphosphorylation and if depletion in Fly occurs it causes tau induced neuropathy .
GO cluster analysis identified several other major up regulated novel DEGs like; CTNNB1, UBE2D1, RAP1A and few major down regulated DEGs like EGFR, MAPK1 and AKT1 which were forming hub nodes.
Among these CTNNB1 (β-catenine-1), a fundamental component of the canonical Wnt signaling pathway that controls cell growth and celladhesion . Nonsense and missense mutations in CTNNB1 were identified in patients with ASD  and intellectual disability (ID) .
UBE2D1 has a crucial role in hepatocellular carcinoma progression, itis one of the family members of E2 ubiquitin conjugating enzyme, mediating the ubiquitination and degradation of tumor suppressor protein p53.
RAP1A, a small G protein similar to Ras oncogene and has role in different cellular processes . Other studies show that RAP1A mediates Glioblastoma cell proliferation  and oral cavity squamous cell carcinoma .
EGFR (Epidermal Growth Factor Receptor (EGFR), a member of the ErbB family of receptor tyrosine kinase (RTK) proteins, is aberrantly expressed in tumors . The ZNF216 (zinc finger 216) in human carcinoma cells has been proved to be a potential regulator of EGFR activity .
MAPK1 (Mitogen-activated protein kinase 1) is a serine/threonine kinase that plays critical roles in several cellular processes like cell proliferation, survival, adhesion, migration via phosphorylation of hundreds of nuclear and cytosolic substrates in the cell. It is a master regulator of stem cell differentiation and is responsible for stem cell fate .
A recent study tells MAPK-RAP1A signalling plays an important function as clinical diagnosis and prognostic value in Hepatocellular carcinoma (HCC), and is related with immune infiltration and clinical prognosis .
AKT1 (Protein kinase B) is a member of AGC family of serine-threonine kinases and transduces signals through the phosphoinositide 3-kinase (PI3K)/AKT cell-signalling cascade. It is involved widely in signal transduction, metabolism, cell-cycle regulation, transcription, cell-proliferation and angiogenesis processes.