Expression and regulation of resistin in osteoblasts and osteoclasts indicate a role in bone metabolism

Abstract

The adipose tissue is the site of expression and secretion of a range of biologically active proteins, called adipokines, for example, leptin, adiponectin, and resistin. Leptin has previously been shown to be expressed in osteoblasts and to promote bone mineralization, whereas adiponectin expression is enhanced during osteoblast differentiation. In the present study we explored the possible role of resistin in bone metabolism. We found that resistin is expressed in murine preosteoclasts and preosteoblasts (RAW 264.7, MC3T3-E1), in primary human bone marrow stem cells and in mature human osteoblasts. The expression of resistin mRNA in RAW 264.7 was increased during differentiation and seemed to be regulated through PKC- and PKA-dependent mechanisms. Recombinant resistin increased the number of differentiated osteoclasts and stimulated NFkappaB promoter activity, indicating a role in osteoclastogenesis. Resistin also enhanced the proliferation of MC3T3-E1 cells in a PKA and PKC-dependent manner, but only weakly interfered with genes known to be upregulated during differentiation of MC3T3-E1 into osteoblasts. All together, our results indicate that resistin may play a role in bone remodeling.

The role of resistin as a regulator of inflammation: Implications for various human pathologies

“…Resistin stimulates osteoclast differentiation and NF-κB activity, the major signaling pathway involved in osteoclastogenesis. The observed, although weak, decrease in the RANKL/OPG mRNA ratio may indicate an indirect inhibitory effect, while an increase in IL-6 secretion may result in a stimulatory effect on osteoclastogenesis [118]. In one study, resistin levels correlated with a marker of bone metabolism, carboxyterminal cross-linked telopeptide of type I collagen (ICTP), while it was inversely related with bone mineral density [101].…”

“…Resistin expression has been found in murine preosteoblasts, preosteoclasts, and in primary human bone marrow stem cells, as well as in mature human osteoblasts [118]. Resistin stimulates osteoclast differentiation and NF-κB activity, the major signaling pathway involved in osteoclastogenesis.…”

Differential proteomic analysis of a human breast tumor and its matched bone metastasis identifies cell membrane and extracellular proteins associated with bone metastasis

“…Major down-regulated proteins in the bone metastatic lesion include apolipoprotein E, whose deficiency has been reported in the context of a reduction of bone formation 50 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 osteolysis 53 , resistin, which is known to increase osteoclastogenesis 54 , and prothrombin, which is overexpressed during osteoclastogenesis in rodents. 55 Among the proteins expressed in the bone metastase and the breast primary lesion, we noticed that the small leucine-rich proteoglycan (SLRP) family was well represented.…”

“…86 31 RETN Resistin ↑ Resistin increased the number of differentiated osteoclasts and stimulated NFkappaB promoter activity, indicating a role in osteoclastogenesis. 54 32 F2 Prothrombin ↑ Prothrombin expression is increased during rodent osteoclastogenesis. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 …”

Metabolizm kostny, osteoprotegeryna i ligand receptora aktywatora czynnika jądrowego-kB a wybrane hormony tkanki tłuszczowej u dziewcząt z jadłowstrętem psychicznym

“…Kanazawa et al [36] demonstrated that ADIPO and AMP kinase activator stimulated the proliferation, differentiation, and mineralisation of MC3T3-E1 cells, while Luo et al [37,38] concluded that ADIPO stimulated human osteoblasts proliferation and differentiation and inhibited OPG expression in human osteoblasts via the MAPK signalling pathway. Thommesen et al [39] found enhanced RES expression in murine osteoclast and osteoblasts precursor cells (RAW 264.7, MC3T3-E1) and in primary human bone marrow stem cells. The expression of resistin mRNA in RAW 264.7, increased during differentiation, seemed to be regulated through PKC-and PKA-dependent mechanisms.…”