The chondrogenic potential of periosteum decreases with age

Abstract

Periosteum contains undifferentiated inesenchymal stem cells that possess the potential for chondrogenesis during cartilage repair and in fracture healing. With aging, the chondrogenic potential of periosteum declines significantly. An organ-culture model was used to investigate the relationship between the chondrogenic potential of periosteum and aging. A total of 736 periosteal explants from the proximal medial tibiae of 82 rabbits, aged 2 weeks to 2 years, were cultured in agarose suspension conditions conductive for chondrogenesis, and analyzed using histomorphometry, collagen typing, wet weight measurement, jH-thymidine and "S-sulfate uptake, autoradiography, and PCNA immunostaining. The rabbits were skeletally mature by 6 months and stopped increasing in weight by 12 months. Chondrogenesis declined significantly with age ( P < 0.0001) and was maximal in the 1.5-2 month-old rabbits, Explants from the 6 month-old rabbits formed 50% less cartilage, and by 12 months chondrogenesis reached a steady state minimal level. In parallel with this decrease in chondrogenic potential similar decreases were measured in 'H-thymidine uptake ( P < 0.0001 ). "S-sulfate uptake ( P = 0.01 17), as well as the thickness ( P < 0.0001) and the total number of cells in the cambium layer of the periosteum ( P < 0.0001 ). Autoradiography with 'H-thymidine and PCNA immunostaining confirmed the measured decrease in proliferative activity in the cambium layer where the chondrocyte precursors reside, although the percentage of proliferating cells did not change significantly with age. The most dramatic change was the marked decrease (87"h) in the thickness and total cell number in the cambium layer of the perisoteum between the 2 and 12 month-old rabbits ( P < 0.05). These data confirm a decline in the chondrogenic potential of periosteum with aging. Thus, one possibility for improving cartilage formation by periosteal transplantation after skeletal maturity would be to stimulate an increase in the total number of cells in the chondrocyte precursor pool early during chondrogenesis.

RETRACTED: The periosteum

“…Periosteal fibroblast number and fibrous layer thickness decrease with age, 127 although atrophy of the fibrous layer is less than that of the cambium layer. 91 Vessel density throughout the periosteum also declines with age but retains the capacity to increase when activated by mechanical loading or fracture repair. 38 These age-induced changes may help explain why periosteal cells from older subjects fail to form mineralized nodules in culture, 85 and why periosteal bone formation rate 40 and responsiveness to hormones and cytokines 95 decline with age.…”

“…Absolute and relative values of total periosteum thickness and the thickness of each layer are decreased. 4,72,91 The main feature of the morphologic changes of cambium layer during aging is almost dramatical decrease 127 and elongation 38 of osteoblasts. This reduction in osteoblast number may contribute to the apparent atrophy and thinning of the cambium layer that occurs with age.…”

“…This reduction in osteoblast number may contribute to the apparent atrophy and thinning of the cambium layer that occurs with age. 91 Periosteal fibroblast number and fibrous layer thickness also decrease with age, 127 although atrophy of the fibrous layer is less than that of the cambium layer. 38,91 This, biologically impaired and reduced periosteum has small reparatory potential with slower response rate on stimulation with cytokines and hormones (longer fracture healing time).…”

“…59 With growth, the periosteum becomes thinner and loses elasticity and firmness. 91 It is especially compliant on tensile forces and tearing which results in the disruption of the periosteum in the level of bone fracture in adults. The periosteum is highly vascularized and innervated and contains large amounts of lymphatic vessels.…”

Human Periosteum Is a Source of Cells for Orthopaedic Tissue Engineering: A Pilot Study

“…Studies have explored the use of periosteal explants [28,29,37] or isolated cells [6,11,22] to generate bone [16,20] or cartilage [10,23,28,37,38]. Factors influencing cell phenotype include sex steroids [41,43], endogenous growth factors [26,45] and mechanical loading environment in vivo [27,42], and isolation [30], culture methods [8,13,20,31,37] and the donor site [14] in vitro.…”