In VivoDistribution of Parathyroid Hormone Receptors in Bone: Evidence that a Predominant Osseous Target Cell Is Not the Mature Osteoblast*

Abstract

Previous studies in vitro and in vivo have demonstrated the presence of receptor sites for PTH on cells of the osteoblast phenotype. Nevertheless, it is unclear whether the diverse functions of this hormone in bone can all be attributed to its interaction with a single cell type. In this study, we have used a radioautographic method to examine the competitive binding of 125I-labeled rat PTH-(1-34) to the long bones of rats in vivo. Our studies confirm the presence of competitive binding to mature osteoblasts and the absence of significant competitive binding to multinucleated osteoclasts. However, by light and electron microscopic radioautographic analysis, the majority of specific competitive PTH binding was present over a cell in the intertrabecular space of the metaphyseal region, which was distinct from the mature osteoblast. This large mononuclear cell with multiple cytoplasmic extensions appeared to interface with both the bone matrix and the microvascular osseous circulation and may provide an additional target to mediate hormonal effects on the skeleton.

Global amplification polymerase chain reaction reveals novel transitional stages during osteoprogenitor differentiation

“…Our results also show that mRNA for PTH1R is expressed continuously through the lineage from early progenitor to mature osteoblast and that it tends to peak as osteoblasts reach maturity and then declines concomitantly with downregulation of osteoblast-specific messages. These observations are different from studies reporting that the highest number of receptors is on relatively undifferentiated osteoblasts, with relatively few on the terminally differentiated mature osteoblast (Rouleau et al, 1988), but are in agreement with other studies in which PTH1R has been demonstrated to be high in the mature osteoblast population (Bos et al, 1996;Suda et al, 1996), and with earlier in situ studies showing the receptor to be present on osteoblasts and its immediate precursors (Lee et al, 1994;Silve et al, 1982). The fact that we find both molecules expressed already in immature progenitors through to more mature osteoblasts support the idea of a widespread autocrine/paracrine function for these molecules during osteoblast development (Lanske and Kronenberg, 1998;Suda et al, 1996).…”

Vitamin D3 differentially regulates parathyroid hormone/parathyroid hormone-related peptide receptor expression in bone and cartilage

“…The distribution of PTHR coding sequences detected in mouse tibiae by in situ hybridization was essentially identical to that of P2-specific sequences, i.e., in chondrocytes extending from the proliferative zone to the upper region of the hypertrophic zone of the growth plate, and in both preosteoblasts and osteoblasts below the growth plate (Fig 5). This is consistent with our previous reports of in vivo binding of PTH and PTHrP to bone and cartilage cells (15,(45)(46)(47). D3 treatment markedly decreased the expression of the PTHR coding region in both preosteoblasts and osteoblasts.…”

Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro.

“…At present, osteocalcin is the only known bone-specific protein produced by osteoblasts (11). This protein is reported to appear in a later stage of osteoblast differentiation (2,34,45), presumably in mature osteoblasts, whereas ALP (2, 34, 45), PTH receptors (29), and type I collagen (31, 34, 45) appear even in less differentiated osteoblasts. Although C26 cells have already acquired a low level of the latter characteristics, but they lack osteocalcin synthesis in an unstimulated state.…”