of the stem cells differentiate into osteoblasts. These osteoblasts lay down a highly vascularized spongy bone tissue in the center. With time, these osteoblasts mature into osteocytes and lay down the hard, dense bony matrix. Mineralization results in the formation of cortical bone. The outermost membranous sheet forms the periosteum (outermost single-layered covering of the bone).
The other form of ossification is endochondral ossification. Bones developed in this manner have an initial model made of hyaline cartilage. This cartilage later ossifies, during the third month of gestation. The outermost layer of hyaline cartilage is infiltrated by blood vessels and osteoblast, leading to formation of periosteum. Osteoblasts then penetrate the cartilage in the diaphysis (shaft of a long bone) and replace it with cancellous bone, forming a primary ossification center. This newly formed cancellous bone is later broken down to form the medullary cavity. The ends of the bones, called epiphyses are the sites of secondary ossification centers, which only produce the spongy bone, and not the medullary cavity. The spongy bone at the secondary center ossifies after birth. A layer of hyaline cartilage is retained over the surface of epiphysis (articular cartilage), and between the epiphysis and diaphysis (epiphyseal cartilage). Articular cartilage forms part of a joint. Epiphyseal cartilage serves as a growth region.
Even though the length of bones stops increasing at a certain point, they are capable of growing in thickness throughout life. The action of bone cells is under the control of hormones and paracrine signaling—the process of communication between adjacent cells. Osteoblast action is stimulated by growth hormone, thyroid hormone, estrogen, and androgens. Osteoclast action is stimulated by a chemical (interleukin-6) secreted by osteoblasts and it is inhibited by the hormone calcitonin.
Figure 1 Structure of a long bone
Source: Blausen Gallery 2014. Wikidiversity Journal of Medicine.
Regeneration
Regeneration is a process by which the cells of living tissues are renewed after any loss or damage to the configuration or functional ability of that specific tissue. This process is essential for a healthy, effective functioning of all the body systems in conjunction with each other. Almost all tissues of the body are capable of regenerating on their own after an injury.
Endogenous bone regeneration is a complicated process that is required for the repair of any bones that might be damaged due to trauma, infection, or malignancy—with this process being most effective in fracture healing. It is affected by environmental factors, and a healthy blood supply is imperative to the intrinsic mechanisms responsible for bone healing. These involve a number of signaling pathways that re-orchestrate the process of intramembranous and endochondral ossification. The osteoprogenitor cells, which arise from the mesenchymal stem cells (MSCs), lie at the root of this entire mechanism. When a portion of bone is damaged or injured due to any reason, the osteoprogenitor cells—contained within the periosteum and the bone marrow—give rise to the osteoblasts, which, after proliferation, deposit the bone matrix around themselves and cause mineralization, forming a new bone in its place. Unlike the soft-tissue regeneration process, bones heal without the formation of a scar, hence ensuring the unhindered functioning of the movement apparatus of the body.
However, there are situations in which the intrinsic ability of the MSCs falls short of that required for a certain condition like a large bone traumatic injury, a serious infection, osteoporosis, the healing required after the resection of a bone tumor, or when the blood supply to the bone is compromised. In these conditions, the botched regeneration effort results in the bones becoming scarred, leading to mal-union. Nowadays, there are multiple methods to enhance this impaired regeneration of bone; some are under intensive research, and some are already being practiced. These include the following.
Bone Grafting. There are three main types of bone grafting techniques: (1) In the autologous bone graft: The graft is taken from bones of the same individual requiring the procedure. The bones used for harvesting of the graft include the mandible, ribs, iliac crest, and the fibula. (2) In the allograft, the graft is obtained from an individual other than the beneficiary. An allograft can also be taken from bone donors after their death. There are three types of an allograft; namely, fresh or fresh-frozen bone, freeze-dried bone, and demineralized freeze-dried bone. (3) The xenograft requires the use of a bone graft taken from an animal source other than the human species.
Distraction Osteogenesis. This method is applicable when there is a large skeletal defect or a fractured bone with separated ends. External fixators, intra-medullary nails, and intra-medullary lengthening devices are all devices that are surgically fixed to the damaged bone, but this is a prolonged treatment and technically is quite demanding.
Mesenchymal Stem Cell Implantation. There is a possibility of utilizing autologous MSCs in regeneration of bones. The process involves isolating and then purifying the MSCs of an individual, expanding them in vitro by producing cultures, and then implanting them into the bone defect with the help of a suitable carrier.
Ammara Iftikhar
Aaiza Iftikhar
Aamir Aslam
Pakistan Medical and Dental Council
See Also: Bone: Cell Types Composing the Tissue; Bone: Existing or Potential Regenerative Medicine Strategies; Bone: Stem and Progenitor Cells in Adults.
Further Readings
Dimitriou, Jones, et al. “Bone Regeneration: Current Concepts and Future Directions.” BMC Medicine, v.9 (2011).
Saladin, Kenneth. “Anatomy and Physiology: The Unity of Form and Function.” New York: McGraw-Hill, 2012.
Soucacos, P. N., E. O. Johnson, and G. Babis. “An Update on Recent Advances in Bone Regeneration.” Injury, v.39/2 (September 2008).
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Bone: Existing or Potential Regenerative Medicine Strategies
Bone is a supporting tough tissue that provides structure to the body and aids movement by cooperating with the muscles. We have over 200 bones in our bodies, forming the skeletal structure and weighing approximately 2 kilograms (kg). Bone is a unique tissue that constantly undergoes remodeling through the period of adult life. Bone defects result from tumor resection, congenital malformations, trauma, fractures, periodontitis, and diseases such as arthritis and osteoporosis. Clinically, healing of fractures is a natural phenomenon in which bone regeneration occurs as part of the healing process. Bone is the only tissue where there is no scar tissue formation in the healing process, and the constant remodeling of the bone is one of the factors that facilitate this regeneration.
Other than the liver, bone is the only organ in the human body that can regenerate. As mentioned above, the ability to regenerate is demonstrated in the human body when a fractured bone uses its potential to regrow and heal itself. Fracture healing takes place in three phases: (1) the reactive phase, in which there is inflammation and granular tissue forms; (2) the reparative phase, in which there is cartilage callus formation and lamellar bone deposition, and (3) the remodeling phase, in which the lamellar
