title: Monocyte chemoattractant protein-1 is a mediator of the anabolic action of parathyroid hormone on bone.
abstract: Parathyroid hormone (PTH) has a significant role as an anabolic hormone in bone when administered by intermittent injection. Previous microarray studies in our laboratory have shown that the most highly regulated gene, monocyte chemoattractant protein-1 (MCP-1), is rapidly and transiently induced when hPTH(1-34) is injected intermittently in rats. Through further in vivo studies, we found that rats treated with hPTH(1-34) showed a significant increase in serum MCP-1 levels 2 hours after PTH injection compared with basal levels. Using immunohistochemistry, increased MCP-1 expression in osteoblasts and osteocytes is evident after PTH treatment. PTH also increased the number of marrow macrophages. MCP-1 knockout mice injected daily with hPTH(1-34) showed less trabecular bone mineral density and bone volume compared with wild-type mice as measured by peripheral quantitative computed tomography (pQCT) and micro-computed tomography (µCT). Histomorphometric analysis revealed that the increase in osteoclast surface and osteoclast number observed with intermittent PTH treatment in the wild-type mice was completely eliminated in the MCP-1 null mice, as well as much lower numbers of macrophages. Consequently, the lack of osteoclast and macrophage activity in the MCP-1 null mice was paralleled by a reduction in bone formation. We conclude that osteoblast and osteocyte MCP-1 expression is an important mediator for the anabolic effects of PTH on bone.
authors.affiliation: Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, NJ, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Tamasi
authors.forename: Anatoliy
authors.initials: A
authors.lastname: Vasilov
authors.forename: Emi
authors.initials: E
authors.lastname: Shimizu
authors.forename: Noah
authors.initials: N
authors.lastname: Benton
authors.forename: Joshua
authors.initials: J
authors.lastname: Johnson
authors.forename: Claudine L
authors.initials: CL
authors.lastname: Bitel
authors.forename: Nigel
authors.initials: N
authors.lastname: Morrison
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Partridge
mesh_terms: D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism*; D018932:Chemokine CCL2 / Q000097:blood / Q000172:deficiency / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013977:Tibia / Q000166:cytology / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D045930:Anabolic Agents; D018932:Chemokine CCL2; D010281:Parathyroid Hormone
keywords: BONE ANABOLISM; BONE TURNOVER; CYTOKINES; MONOCYTE CHEMOATTRACTANT PROTEIN (MCP-1); PARATHYROID HORMONE (PTH)