Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: A possible role of interleukin-6 in osteoclastogenesis

Löwik, Clemens W.G.M.; Pluijm, Gabri van der; Bloys, H.; Hoekman, K.; Bijvoet, O. L. M.; Aarden, Lucien A.; Papapoulos, Socrates E.

doi:10.1016/0006-291x(89)90851-6

Cited by 362 publications

(149 citation statements)

References 16 publications

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“…IL-6 mRNA expression in stromal cells reaches its peak by 1 hr and returns to the basal level by 2 hr after PTH administration. The similarity of the time course of PTHinduced IL-6 mRNA expression between previous in vitro studies with osteoblastic cells [4,11] and our in situ hybridization data are consistent with the notion that stromal cells that express IL-6 transcripts in response to PTH in vivo belong to the osteoblast lineage. Moreover, since IL-6 mRNA is not detected in mature osteoblasts at any of the time points (0 to 6 hr) examined after PTH injection, it is speculated that osteoblast precursors are the principal bone cells that manifest an IL-6 response to PTH in vivo, although we do not exclude the possibility that these IL-6 expressing cells belong to other cell lineage such as the osteoclast lineage.…”

supporting

confidence: 90%

“…The time course of PTHinduced IL-6 mRNA expression in vivo is similar to the previously reported in vitro data with clonal osteoblastic cell lines and primary osteoblasts [3,4,11], and exhibits a typical "immediate early gene response" pattern [16], i.e. transient and brief expression with its peak ranging from 1/4 to 1 hr.…”

supporting

confidence: 82%

“…IL-6 gene expression in both clonal osteoblastic cell lines and primary osteoblasts is stimulated by PTH in vitro [3,4,11], and PTH increases circulating levels of IL-6 [6] as well as IL-6 expression in bone in vivo [13]. In addition, PTH-activation of osteoclasts is partially blocked by anti-IL-6 receptor antibody in vitro [5], and PTH's bone resorbing activity in vivo also dramatically decreases in the absence or inactivation of IL-6 in mice [6].…”

mentioning

confidence: 99%

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Parathyroid Hormone Induces Interleukin-6 Gene Expression in Bone Stromal Cells of Young Rats.

Chiba

Un-No

Neer

et al. 2002

The Journal of Veterinary Medical Science

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ABSTRACT. To test the hypothesis that parathyroid hormone (PTH) regulates interleukin-6 (IL-6) expression locally in bone, the expression of IL-6 mRNA was examined by in situ hybridization after a subcutaneous injection of human PTH (225 µg/kg) in 4-week old rats. Whereas IL-6 mRNA was not detected at the basal status, it was transiently detected in a subpopulation of stromal cells in the intertrabecular region of the metaphyses from 1/2 to 1 hr after PTH injection. Contrastingly, IL-6 transcripts were not detected in other cell populations at any time points examined. Since IL-6 is a known activator of osteoclasts, these results are consistent with the hypothesis that PTH stimulates the local IL-6 synthesis in stromal cells to indirectly activate osteoclasts. KEY WORDS: interleukin-6, parathyroid hormone, stromal cell.

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supporting

confidence: 90%

supporting

confidence: 82%

mentioning

confidence: 99%

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Parathyroid Hormone Induces Interleukin-6 Gene Expression in Bone Stromal Cells of Young Rats.

Chiba

Un-No

Neer

et al. 2002

The Journal of Veterinary Medical Science

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“…These findings agree with those of other in vivo and in vitro studies. 4,8,9,12,13,15,16,21,28-35. IL-1 and IL-6 modulate the function of many cell lines including monocytes, macrophages, fibroblasts, osteoblasts, osteoclasts, and T and B lymphocytes, 4,13,[36][37][38][39][40][41] as well as the effects of IL-2 and TNF␣; the latter cytokine is also proinflammatory. Thus, IL-1 and IL-6 have important roles in modulating immune functions and the growth, differ- entiation and remodelling of mesenchymal tissue.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, IL-1 and IL-6 are important in osteoclast-mediated bone resorption since they stimulate directly the differentiation and maturation of osteoclast precursors. [36][37][38][39][40][41] TGF␤ is generally an antiinflammatory, immune-suppressant cytokine, important in the repair and remodelling of mesenchymal tissue. 38 It also has a significant role in wound healing, facilitates the formation of the extracellular matrix by osteoblasts and other cells, and inhibits osteoclast function.…”

Section: Discussionmentioning

confidence: 99%

Cellular profile and cytokine production at prosthetic interfaces

Goodman¹,

Huie

Song³

et al. 1998

The Journal of Bone and Joint Surgery. British volume

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T he tissues surrounding 65 cemented and 36 cementless total joint replacements undergoing revision were characterised for cell types by immunohistochemistry and for cytokine expression by in situ hybridisation.We identified three distinct groups of revised implants: loose implants with ballooning radiological osteolysis, loose implants without osteolysis, and well-fixed implants. In the cemented series, osteolysis was associated with increased numbers of macrophages (

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Parathyroid hormone (1-34)–mediated interleukin-6 induction

et al. 1997

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Parathyroid hormone (PTH) functions in part by regulating osteoblast cytokine expression. We recently demonstrated that PTH induced a rapid and transient increase in interleukin-6 (IL-6) mRNA expression in rat bones in vivo. To determine the molecular basis of this effect, we analyzed the human IL-6 promoter fused (-1,179 to +9) with the chloramphenicol acetyltransferase (CAT) reporter gene in stable transfections into human osteoblast-like osteosarcoma SaOS-2 cells. We compared the effects of PTH on IL-6 expression with adenylate cyclase activator forskolin, PKC activator phorbol 12-myristate 13-acetate (PMA), calcium ionophore A23187, interleukin-1 alpha (IL-1 alpha), prostaglandin E-2 (PGE-2), RS-66271 (a parathyroid hormone-related peptide analog), and platelet-derived growth factor-BB (PDGF-BB). Analyses of cell clones showed that IL-6 promoter expression was extremely low in the unstimulated state. Exposure to PTH (0.001-100 nM) for 12 h stimulated CAT expression in a dose-dependent manner (200-500% of control). Treatment with IL-1 alpha was more potent than PTH in inducing transcription of the IL-6 promoter (900-1,000%). Activation of the cAMP-PKA pathway by treatment with forskolin induced a comparable level of induction with PTH. Together, the effects of PTH and forskolin were additive. RS-66271, previously shown to have PTH-like effects, induced a comparable level of IL-6 promoter expression. When examined together, PTH+RS-66271 effects were comparable to PTH effects alone. Exposure to PGE-2, PMA, PDGF-BB, or A23187 for 12 h did not significantly alter IL-6 promoter expression. These results demonstrate PTH, forskolin, the PTHrP analog RS-66271, and IL-1 alpha stimulate IL-6 expression by stimulating gene transcription. The response to forskolin suggests that the messenger system mediated by PKA is sufficient to induce IL-6 expression.

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Parathyroid hormone (PTH) and PTH-like protein (PLP) stimulate interleukin-6 production by osteogenic cells: A possible role of interleukin-6 in osteoclastogenesis

Cited by 362 publications

References 16 publications

Parathyroid Hormone Induces Interleukin-6 Gene Expression in Bone Stromal Cells of Young Rats.

Parathyroid Hormone Induces Interleukin-6 Gene Expression in Bone Stromal Cells of Young Rats.

Cellular profile and cytokine production at prosthetic interfaces

Parathyroid hormone (1-34)–mediated interleukin-6 induction

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