If we can figure out how to grow via articular cartilage that will be a lot easier than to try to create neo-growth plates.
Spatial Regulation of Gene Expression During Growth of Articular Cartilage in Juvenile Mice.
“In juvenile mammals, the epiphyses of long bones grow by chondrogenesis within the articular cartilage. A bWe used laser-capture microdissection to isolate chondrocytes from the superficial, middle, and deep zones of growing tibial articular cartilage in the 1-wk old mouse and then investigated expression patterns by microarray. To identify molecular markers for each zone of the growing articular cartilage, we found genes showing zone-specific expression and confirmed by real-time PCR and in situ hybridization.Bioinformatic analyses implicated ephrin receptor signaling, Wnt signaling, and BMP signaling in the spatial regulation of chondrocyte differentiation during growth. Molecular markers were identified for superficial (e.g. Cilp, Prg4), middle (Cxcl14, Tnn), and deep zone (Sfrp5, Frzb). Comparison between juvenile articular and growth plate cartilage revealed that the superficial-to-deep zone transition showed similarity with the hypertrophic-to-resting zone transition{This is interesting, the study speculates that both the resting zone and deep zone may come from the same pool of epiphyseal chondrocytes}.ConclusionsLaser capture microdissection combined with microarray analysis identified novel signaling pathways that are spatially regulated in growing mouse articular cartilage and revealed similarities between the molecular architecture of the growing articular cartilage and that of growth plate cartilage.”
“While cell proliferation occurs sparingly in adult articular cartilage, it is much more common in juvenile articular cartilage. Growth of the articular cartilage reportedly occurs appositionally from the articular surface, suggesting that the SZ may contain actively dividing chondrocytes, or a progenitor cell population that is capable of generating new chondrocytes”<-these properties could be exploited to induce new longitudinal bone growth
“DZ[Deep Zone Articular Cartilage] expressed a high level of Wnt5b, which promotes chondrogenesis and inhibits hypertrophy ”
The development of articular cartilage: evidence for an appositional growth mechanism
“It is well-established that cartilage grows by a combination of matrix secretion, cell hypertrophy and cell proliferation. The extent to which this growth is by appositional, as opposed to interstitial mechanisms, however, remains unclear. Using the knee joints of the marsupial Monodelphis domestica to study cartilage growth, we have combined an immunohistochemical study of the TGF-β family of cartilage growth and differentiation factors between 30 days postpartum to 8 months, together with a stereological analysis of cartilage morphology during growth. Furthermore, to gain an insight into the generation of the characteristic zones within cartilage, we have examined the effects of intra-articular administration of bromodeoxyuridine, an agent that is incorporated into DNA during cell division and blocks further cell cycling. During early growth, TGF-β2 and -β3 were widely expressed but TGF-β1 was less so. After the formation of the secondary centre of ossification, all isoforms became more restricted to the upper half of the tissue depth and their distribution was similar to that previously described for IGFs, and PCNA-positive cells. Stereological analysis of tissue sections from the femoral condylar cartilage at 3 and 6 months showed that there was a 17% increase in total cartilage volume but a 31% decrease in cell density on a unit volume basis. Finally, cell-cycle perturbation with BrDU, which was injected into the knee joints of 3-month-old animals and analysed 1 and 4 months post-injection, revealed that the chondrocytes occupying the transitional zone were depleted 1 month post-injection, resulting in thinning of the articular cartilage. This effect was reversed 4 months post-injection. Immunohistochemical analysis revealed that BrDU-treatment altered the expression patterns of all TGF-β isoforms, with a marked reduction in labelling of TGF-β1 and -β3 isoforms in the upper half of the cartilage depth. Overall, the data lends further support to the notion of articular cartilage growing by apposition from the articular surface rather than by interstitial mechanisms.”
Articular cartilage and joint development from embryogenesis to adulthood
“Within each synovial joint, the articular cartilage is uniquely adapted to bear dynamic compressive loads and shear forces throughout the joint’s range of motion.”
“Early studies suggested that a region of proliferating cells “subjacent to the gliding surface of the joint” was responsible for interstitial growth of articular cartilage and increasing thickness of the articular surface. In this same study, Mankin and collaborators found that proliferation continued within deeper regions of the tissue and adjacent to the calcified cartilage, but ceased within the sub-superficial zone at later stages of postnatal growth. The presence of these two proliferative cell regions was confirmed by tritiated thymidine incorporation in the articular cartilage of immature rabbits. Later, Archer and collaborators confirmed the presence of a proliferative cell region in the superficial zone, suggesting that these cells were primarily responsible for the appositional growth and thickening of the articular cartilage postnatally”
“lateral expansion of the articular surface could be attributed to proliferation of cells within the superficial zone that would also give rise to daughter cells in a more rapidly proliferating cell population in the deeper zones leading presumably to vertical tissue growth.”
“In the growth plate, tremendous increases in chondrocyte volume contribute greatly to lengthening of long bones”
“chondrocyte volume in the middle and deep layers increased by over 8 fold from birth to 2 months of age, while overall decreases in cell density reflecting an increase in extracellular matrix production occurred during this same period.”