1. Chapter 26: Parathyroid Hormone-Related Protein
John J. Wysolmerski

2. From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th Edition.
Figure 1
Figure 1 PTHrP and Ihh act as part of a negative feedback loop regulating chondrocyte proliferation and differentiation. The chondrocyte differentiation program proceeds from undifferentiated chondrocytes at the end of the bone, to proliferative chondrocytes within the columns, and to prehypertrophic and terminally differentiated hypertrophic chondrocytes nearest the primary spongiosum. PTHrP is made by undifferentiated and proliferating chondrocytes at the ends of long bones. It acts through PTH1R on proliferating and prehypertrophic chondrocytes to delay their differentiation, maintain their proliferation and delay the production of Ihh, which is made by hypertrophic cells (1). Ihh, in turn, increases the rate of chondrocyte proliferation (2) and stimulates the production of PTHrP at the ends of the bone (3). Ihh also acts on perichondrial cells to generate osteoblasts of the bone collar (4). (Reprinted with permission from Macmillan Publishers: Kronenberg HM 2003 Developmental regulation of the growth plate. Nature 423:332–336.)
Figure 1 PTHrP and Ihh act as part of a negative feedback loop regulating chondrocyte proliferation and differentiation. The chondrocyte differentiation program proceeds from undifferentiated chondrocytes at the end of the bone, to proliferative chondrocytes within the columns, and to prehypertrophic and terminally differentiated hypertrophic chondrocytes nearest the primary spongiosum. PTHrP is made by undifferentiated and proliferating chondrocytes at the ends of long bones. It acts through PTH1R on proliferating and prehypertrophic chondrocytes to delay their differentiation, maintain their proliferation and delay the production of Ihh, which is made by hypertrophic cells (1). Ihh, in turn, increases the rate of chondrocyte proliferation (2) and stimulates the production of PTHrP at the ends of the bone (3). Ihh also acts on perichondrial cells to generate osteoblasts of the bone collar (4). (Reprinted with permission from Macmillan Publishers: Kronenberg HM 2003 Developmental regulation of the growth plate. Nature 423:332–336.)

3. From the Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 7th Edition.
Figure 2
Figure 2 PTHrP regulates mesenchymal cell fate during embryonic mammary development. (A) During normal mammary development, PTHrP is secreted by epithelial cells within the forming mammary bud (dark circles) and interacts with the immature dermal mesenchyme (gray ovals) to induce formation of the dense mammary mesenchyme (light squares). These cells, in response to PTHrP, maintain the fate of the mammary epithelial cells, initiate branching morphogenesis, and induce the formation of the specialized nipple skin (dark squares). (B) In PTHrP- or PTH1R-knockout embryos, the mammary bud forms, but the mammary mesenchyme does not. As a result, the mammary epithelial cells revert to an epidermal fate (dark ovals), morphogenesis fails, and the nipple never forms. (Adapted with permission from Company of Biologists: Foley J, Dann P, Hong J, Cosgrove J, Dreyer BE, Rimm D, Dunbar, ME, Philbrick WM, Wysolmerski JJ 2001 Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development 128:513–525.)
Figure 2 PTHrP regulates mesenchymal cell fate during embryonic mammary development. (A) During normal mammary development, PTHrP is secreted by epithelial cells within the forming mammary bud (dark circles) and interacts with the immature dermal mesenchyme (gray ovals) to induce formation of the dense mammary mesenchyme (light squares). These cells, in response to PTHrP, maintain the fate of the mammary epithelial cells, initiate branching morphogenesis, and induce the formation of the specialized nipple skin (dark squares). (B) In PTHrP- or PTH1R-knockout embryos, the mammary bud forms, but the mammary mesenchyme does not. As a result, the mammary epithelial cells revert to an epidermal fate (dark ovals), morphogenesis fails, and the nipple never forms. (Adapted with permission from Company of Biologists: Foley J, Dann P, Hong J, Cosgrove J, Dreyer BE, Rimm D, Dunbar, ME, Philbrick WM, Wysolmerski JJ 2001 Parathyroid hormone-related protein maintains mammary epithelial fate and triggers nipple skin differentiation during embryonic breast development. Development 128:513–525.)