In the studies of physeal briding, the Zone of ranvier's unobstruction was critical for normal longitudinal bone growth without angular deformities. The zone of ranvier is also placed on the longitudinal side of the bone so may be key to LSJL. Studying how much the zone of ranvier is maintained post diaphyseal/epiphyseal fusion may be key to forming new growth plates.
Here's an image of the zone of ranvier:
From Normal Bone Formation.
"The growth plate may be divided anatomically into three components: a cartilaginous component, itself divided into various histologic zones; a bony component, or metaphysis; and a fibrous component surrounding the periphery of the plate comprising the groove of Ranvier and the perichondrial ring of LaCroix."
"The epiphyseal artery supplies the epiphysis, or the secondary center of ossification, which itself is not part of the growth plate. Small branches arise at right angles to the main epiphyseal artery in the epiphysis and pass through small cartilage canals in the reserve zone to terminate at the top of the cell columns in the proliferative zone. Each small branch from the epiphyseal artery arborizes in rakelike fashion to supply the top portion of from four to ten cell columns. The proliferative zone, therefore, is well supplied with blood. None of the branches from the epiphyseal arteries penetrate the cartilage portion of the growth plate beyond the uppermost part of the proliferative zone; that is, no vessels pass through the proliferative zone to supply the hypertrophic zone."
"The reserve zone lies immediately adjacent to the secondary bony epiphysis. Various terms have been applied to this zone, including resting zone, zone of small-size cartilage cells, and germinal zone. However, these cells are not resting, are not small in comparison with the cells in the proliferative zone, and they are not germinal cells. They appear to store lipid and other materials and perhaps are held in reserve for later nutritional requirements. If that is true, the term reserve zone may be appropriate. The cells in this zone are spherical, exist singly or in pairs, are relatively few when compared with the number of cells in other zones, and are separated from each other by more extracellular matrix than are cells in any other zone. The cells in the reserve zone are approximately the same size as the cells in the proliferative zone. The cytoplasm exhibits a positive staining reaction for glycogen. These cells contain abundant endoplasmic reticulum, a clear indication that they are actively synthesizing protein. They contain more lipid bodies and vacuoles than do cells in other zones but contain less glucose-6-phosphate dehydrogenase, lactic dehydrogenase, malic dehydrogenase, and phosphoglucoisomerase. The zone also contains the lowest amount of alkaline and acid phosphatase, total and inorganic phosphate, calcium, chloride, potassium, and magnesium. The matrix in the reserve zone contains less lipid, glycosaminoglycan, protein polysaccharide, moisture, and ash than the matrix in any other zone. It exhibits less incorporation of radiosulfur (35S) than any other zone and also shows less Iysozyme activity than the other zones. It contains the highest content of hydroxyproline of any zone in the plate. Collagen fibrils in the matrix exhibit random distribution and orientation. Matrix vesicles are also seen in the matrix, but they are fewer than in other zones. The matrix shows a positive histochemical reaction for the presence of a neutral mucopolysaccharide or an aggregated proteoglycan."
Another image of the Zone of Ranvier and LaCroix:
"The perichondrial ring is a dense fibrous band that encircles the growth plate at the bone-cartilage junction and in which collagen fibers run vertically, obliquely, and circumferentially. It is continuous at one end with the group of fibroblasts and collagen fibers in the ossification groove and at the other end with the periosteum and subperiosteal bone of the metaphysis. In rodents, rabbits, and dogs, the innermost layer of the perichondrial ring consists of bone that may or may not be attached to the subperiosteal bone of the metaphysis. This cylindrical sheath of bone may not be present in all species at all ages in all growth plates. For instance, it is not present in the proximal femur in the human at any age. " Whether or not bone is present in the perichondrial ring, there is no doubt that the ring provides mechanical support for the otherwise weak bone-cartilage junction of the growth plate"
If we can somehow prove that the zone of Ranvier is retained post fusion then that would be a huge breakthrough for forming new growth plates.
Identification of a stem cell niche in the zone of Ranvier within the knee joint.
The periphysis and its effect on the metaphysis: I. Definition and normal radiographic pattern
"The zone of Ranvier and the ring of LaCroix, together with the membranous bone bark they produce, are termed the periphysis in order to emphasize their normal effect (the metaphyseal collar) on the metaphysis of the infant and young child. In the first 7 years of life, the normal collar at the wrist is 1-3 mm wide. The step-off between the metaphyseal collar and the curvilinear metaphysis, at the margin of the periphysis, should not be mistaken for abuse fracture. The periphyseal bone bark may be radiologically visible at the edge of the physis at the distal ulna in 9% of infants and should not be mistaken for fracture or rickets."
"The periphysis surrounds the growth plate (physis) of tubular bones and also the most recently formed several millimeters of metaphysis in infants. It is a fibrochondroosseous structure that (a) appears to maintain the transverse diameter of the physis and at the same time (b) allows gradual transverse growth of the same physis. That portion of the periphysis adjacent to the physis has been described under the names zone or groove of Ranvier, that portion adjacent to the metaphysis, as the
ring of LaCroix.
Histologically, the Ranvier and LaCroix zones are a single structure; both lay down a continuous thin layer of bone, termed bone bark, centrally at the periphery of the physis and metaphysis. This bone bark is produced by membranous, rather than enchondral, bone formation. In the first several years of life that portion of the metaphysis surrounded by the periphysis has a flat, longitudinally directed periphery on radiographs, rather than a smooth curved contour characteristic of the margins of other portions of the metaphysis. The result is the short metaphyseal collar"
"The periphysis [restrains] longitudinal widening of the physis."
Cartilage Tissue Engineering; the search for chondrogenic progenitor cells and associated signalling pathways
"Stem cells [are] not only in the articular cartilage but also in the groove of Ranvier located in the periphery of the epiphyseal growth plate.
The groove of Ranvier exhibited properties as a stem cell niche structure. Further biopsies
from human normal articular cartilage, as well as regenerated and repaired cartilage after ACI
were studied. The human normal articular cartilage demonstrated expression of the stem cell
associated markers STRO-1 and Bcrp1 in cells in the superficial zone, and activity of the
fundamental Wnt (Wingless-related proteins) and Notch signalling pathways. The distribution
showed a distinct zonal pattern in the normal cartilage. In biopsies from regenerated cartilage
with almost normal histological architecture, the markers and pathways studied demonstrated a
distinct zonal pattern similar to that in normal cartilage."
"in articular cartilage there are subpopulations of cells with mesenchymal stem cell properties"
"From the lateral plate mesoderm, undifferentiated mesenchymal cells begin to migrate to areas destined to become bone, followed by tight packing of the cells, known as mesenchymal condensation. The cartilage anlagen for the future skeletal elements have now formed. Cellular condensation is associated with increased cell to cell contact and increased cell to matrix interaction. Molecules taking part in the intercellular communication are e.g. neural cell adhesion molecule (N-CAM), Ncadherin, tenascin, versican, fibronectin and gap junctions (connexin 42 and 43),"
"The first sign of joint formation is the appearance of an interzone. The interzone cells gives rise to the articular layer of the future long bones while the chondrocytes developing from the mesenchymal condensation are assumed to be a part of epiphyseal growth plate and to take part in endochondral ossification, these cells are called transient chondrocytes. It has been unclear whether the interzone cells derive from transdifferentiation of local prechondrocytes into interzone cells or if there is migration of mesenchymal cells into the joint site, or a combination"
"It[perichondrial groove of Raniver] is a circumferential anatomical structure in the periphery of the epiphyseal growth plate and consists of the zone of Ranvier and the ring of LaCroix. It is a well defined structure in the growing skeleton. In the adult it is assumed to be integrated with the periosteum however, this has not been well explored in the adult human being."
"Markers associated with and suggested to define possible stem cells or progenitor cells in mesenchymal tissue and also, in some cases, in adult cartilage are CD105(Endoglin), CD166 (Alcam) and FGFR3 (Fibroblast Growth Factor receptor 3)"
ID1 and ID3 are involved in the proliferation of adult articular chondrocytes.
"A significant decrease in DNA synthesis was noticed when antisense nucleotides against Id1 and Id3 were added, both in normal chondrocytes and chondrosarcoma cells."
"Progenitor cells exist in the perichondrial groove of Ranvier and in the articular cartilage of rabbits (IV)"
"The markers associated with stem cells/progenitor cells and stem cell niches: Stro-1, Notch1, Patched, Jagged1, BMPr1a, 1-Integrin and N-cadherin"
"Progenitor cells exist in the knee of sexually mature rabbits and are mainly located to the perichondrial groove of Ranvier. Progenitor cells have also been detected in small numbers dispersed throughout the articular cartilage."
"The groove of Ranvier in the joint is a potential stem cell niche"