Calgranulin

Calgranulin is used to remove kidney stones which can occur via excessive calcificationn in the kidney.  Calgranulin may be a way to deossify the bone allowing for new growth plate formation.  S100A8/S100A9/S100A12 genes are all associated with calgranulin.


S100A8/S100A9 and their association with cartilage and bone.

"S100A8 and S100A9 are calcium-binding proteins expressed in myeloid cells and are markers of numerous inflammatory diseases in humans. S100A9 has been associated with dystrophic calcification in human atherosclerosis. S100A8 and S100A9 [are expressed] in murine and human bone and cartilage cells. Only S100A8 was seen in preosteogenic cells whereas osteoblasts had variable, but generally weak expression of both proteins.  S100A8 and S100A9 were prominent in osteoclasts. S100A8 was expressed in alkaline phosphatase-positive hypertrophic chondrocytes, but not in proliferating chondrocytes within the growth plate where the cartilaginous matrix was calcifying. S100A9 was only evident in the invading vascular osteogenic tissue penetrating the degenerating chondrocytic zone adjacent to the primary spongiosa, where S100A8 was also expressed. Whilst, S100A8 has been shown to be associated with osteoblast differentiation, both S100A8 and S100A9 may contribute to calcification of the cartilage matrix and its replacement with trabecular bone, and to regulation of redox in bone resorption."

"S100A4{up in LSJL} was found in differentiating osteoblasts and was shown to diminish bone matrix mineralization. S100A2 was detected in chondrocytes within calcifying areas of epiphyseal cartilage suggesting its involvement in cartilage calcification"

"low concentrations of H2O2 or O2− accelerate resorption by osteoclasts and HOCl and hydroxyl radicals can degrade proteoglycans and fragment collagen. HOCl can also alter matrix metalloproteinase (MMP) activity by inactivating tissue inhibitors of MMP and activating certain MMPs "

According to Induction of nuclear factor-κB responses by the S100A9 protein is Toll-like receptor-4-dependent., S100A9 activates NFkappaB via TLR4.

There are several osteoarthritis studies that suggests that S100A8/S100A9 degrade cartilage as well as bone.

Microarray profile of gene expression during osteoclast differentiation in modelled microgravity.

"Microgravity (µXg) leads to a 10-15% loss of bone mass in astronauts during space flight. Osteoclast (OCL) is the multinucleated bone-resorbing cell. In this study, we used the NASA developed ground-based rotating wall vessel bioreactor (RWV), rotary cell culture system (RCCS) to simulate µXg conditions and demonstrated a significant increase (2-fold) in osteoclastogenesis compared to normal gravity control (Xg). Gene expression profiling of RAW 264.7 OCL progenitor cells in modelled µXg by Agilent microarray analysis revealed significantly increased expression of critical molecules such as cytokines/growth factors, proteases and signalling proteins, which play an important role in enhanced OCL differentiation/function. Transcription factors such as c-Jun{up}, MITF and CREB implicated in OCL differentiation are upregulated; however no significant change in the levels of NFATc1 expression in preosteoclast cells subjected to modelled µXg. We also identified high-level expression of calcium-binding protein, S100A8 (calcium-binding protein molecule A8/calgranulin A) in preosteoclast cells under µXg. Furthermore, modelled µXg stimulated RAW 264.7 cells showed elevated cytosolic calcium (Ca(2+)) levels/oscillations compared to Xg cells. siRNA knock-down of S100A8 expression in RAW 264.7 cells resulted in a significant decrease in modelled µXg stimulated OCL differentiation. We also identified elevated levels of phospho-CREB in preosteoclast cells subjected to modelled µXg compared to Xg."

"In space, astronauts are exposed to µXg; 0.08–0.008g rather than Earths inherent gravity of 1g. "

"isolated fetal mouse long bones under near weightless conditions showed decreased mineralization and increased calcium release"

" µXg has been reported to reduce osteoblast life-span and enhance IL-6{up} gene expression, thereby decreasing osteoblast activity and increasing OCL activity to contribute to bone loss associated with weightlessness"

Genes upregulated by microgravity in osteoclasts also upregulated in LSJL:

Pdpn

IL33

CCL24

Edil3

Ppfibp2{down}
Anxa3{down}
Socs3
Pbxip{down}
Vav3{down}
Creb3l1
Mall
Jam2
Masp1
Itpr3{down}
Cacna2d2{down}
Abca9{down}

Down:
Estrogen Receptor Beta(as ESR2){up}

p58 repressor(as Prkrir)