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Ossification of the mammalian metatarsal: proliferation and differentiation in the presence/absence of a defined growth plate

Reno, Philip Louis

Abstract Details

2006, PHD, Kent State University, School of Biomedical Sciences.
The significant variation within wildtype animals is an underutilized resource for studying skeletal development. In the mammalian metatarsal one end forms a growth plate and secondary center of ossification as in other long bones, however the opposite end undergoes direct ossification in a manner more similar to short bones. Thus, the metatarsal can serve as a model to explore the signals and factors that specify growth plate formation in the vertebrate skeleton. In pursuit of this goal I first compared the patterns of chondrocyte differentiation and proliferation during growth plate formation and direct ossification of an age series of mouse metatarsals. As in the human, both growth plate formation and direct ossification are easily discernable in the mouse metatarsal. In addition, growth plate formation is characterized by a region of peak of proliferation corresponding to reserve zone chondrocytes that distinguishes it from both established growth plates and direct ossification. Second, immunohistochemisty reveals that patterns of PTHrP and PTH/PTHrP-receptor are indistinguishable at each end of the metatarsal suggesting PTHrP signaling is not specific to growth plates. In contrast, the distribution of Patched, the Ihh receptor, is highly variable during growth plate formation and appears to co-localize to regions of increased proliferation, suggesting a potential role for Ihh signaling in specifying growth plate formation. Third, a comparative analysis of metapodial ossification between mice and alligators (Alligator mississippiensis) reveals similar proliferative patterns and protein expression during growth plate formation and within established growth plates, indicating that both species share common mechanisms of chondrocyte regulation. However, unlike mice, alligators establish growth plates at both ends of their metapodials. Phylogenetic analysis reveals that the direct ossification of one epiphysis and reliance on a single growth plate is restricted to eutherians and marsupials and thus is a shared derived character (synapomorphy) of placental mammals. Finally, mouse metatarsals raised in culture continue to undergo growth plate formation and direct ossification at its respective ends, demonstrating that chondrocytes themselves have the intrinsic capacity to dictate these processes in the absence of normal systemic (hormonal) signals and mechanical environment.
C. Lovejoy (Advisor)
167 p.

Recommended Citations

Citations

  • Reno, P. L. (2006). Ossification of the mammalian metatarsal: proliferation and differentiation in the presence/absence of a defined growth plate [Doctoral dissertation, Kent State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=kent1153160254

    APA Style (7th edition)

  • Reno, Philip. Ossification of the mammalian metatarsal: proliferation and differentiation in the presence/absence of a defined growth plate. 2006. Kent State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=kent1153160254.

    MLA Style (8th edition)

  • Reno, Philip. "Ossification of the mammalian metatarsal: proliferation and differentiation in the presence/absence of a defined growth plate." Doctoral dissertation, Kent State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=kent1153160254

    Chicago Manual of Style (17th edition)