Bone Marrow Anatomy And Physiology PdfBy Jackson M. In and pdf 28.04.2021 at 20:57 6 min read
File Name: bone marrow anatomy and physiology .zip
From birth to early adolescence, the majority of our bone marrow is red marrow.
- Bone Marrow and Blood Cell Development
- Physiology of normal bone marrow
- Bone marrow and the immune system
Parents can learn about bone marrow and the immune system, as they prepare for their child's blood and marrow transplant BMT. Bone marrow is the spongy tissue inside our bones.
Bone Marrow and Blood Cell Development
Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local e. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis. Recently, it has been recognized that, during bone remodeling, there are an intricate communication among bone cells.
For instance, the coupling from bone resorption to bone formation is achieved by interaction between osteoclasts and osteoblasts.
Moreover, osteocytes produce factors that influence osteoblast and osteoclast activities, whereas osteocyte apoptosis is followed by osteoclastic bone resorption. The increasing knowledge about the structure and functions of bone cells contributed to a better understanding of bone biology.
It has been suggested that there is a complex communication between bone cells and other organs, indicating the dynamic nature of bone tissue.
In this review, we discuss the current data about the structure and functions of bone cells and the factors that influence bone remodeling. Bone is a mineralized connective tissue that exhibits four types of cells: osteoblasts, bone lining cells, osteocytes, and osteoclasts [ 1 , 2 ]. Bone exerts important functions in the body, such as locomotion, support and protection of soft tissues, calcium and phosphate storage, and harboring of bone marrow [ 3 , 4 ]. Despite its inert appearance, bone is a highly dynamic organ that is continuously resorbed by osteoclasts and neoformed by osteoblasts.
There is evidence that osteocytes act as mechanosensors and orchestrators of this bone remodeling process [ 5 — 8 ]. The function of bone lining cells is not well clear, but these cells seem to play an important role in coupling bone resorption to bone formation [ 9 ]. Bone remodeling is a highly complex process by which old bone is replaced by new bone, in a cycle comprised of three phases: 1 initiation of bone resorption by osteoclasts, 2 the transition or reversal period from resorption to new bone formation, and 3 the bone formation by osteoblasts [ 10 , 11 ].
This process occurs due to coordinated actions of osteoclasts, osteoblasts, osteocytes, and bone lining cells which together form the temporary anatomical structure called basic multicellular unit BMU [ 12 — 14 ].
Normal bone remodeling is necessary for fracture healing and skeleton adaptation to mechanical use, as well as for calcium homeostasis [ 15 ]. On the other hand, an imbalance of bone resorption and formation results in several bone diseases. For example, excessive resorption by osteoclasts without the corresponding amount of nerformed bone by osteoblasts contributes to bone loss and osteoporosis [ 16 ], whereas the contrary may result in osteopetrosis [ 17 ].
Thus, the equilibrium between bone formation and resorption is necessary and depends on the action of several local and systemic factors including hormones, cytokines, chemokines, and biomechanical stimulation [ 18 — 20 ]. Recent studies have shown that bone influences the activity of other organs and the bone is also influenced by other organs and systems of the body [ 21 ], providing new insights and evidencing the complexity and dynamic nature of bone tissue.
In this review we will address the current data about bone cells biology, bone matrix, and the factors that influence the bone remodeling process.
Moreover, we will briefly discuss the role of estrogen on bone tissue under physiological and pathological conditions. These cells show morphological characteristics of protein synthesizing cells, including abundant rough endoplasmic reticulum and prominent Golgi apparatus, as well as various secretory vesicles [ 22 , 23 ]. As polarized cells, the osteoblasts secrete the osteoid toward the bone matrix [ 24 ] Figures 1 a , 1 b , and 2 a.
Osteoblasts are derived from mesenchymal stem cells MSC. The commitment of MSC towards the osteoprogenitor lineage requires the expression of specific genes, following timely programmed steps, including the synthesis of bone morphogenetic proteins BMPs and members of the Wingless Wnt pathways [ 25 ]. The expressions of Runt-related transcription factors 2, Distal-less homeobox 5 Dlx5 , and osterix Osx are crucial for osteoblast differentiation [ 22 , 26 ]. Additionally, Runx2 is a master gene of osteoblast differentiation, as demonstrated by the fact that Runx2-null mice are devoid of osteoblasts [ 26 , 27 ].
Once a pool of osteoblast progenitors expressing Runx2 and ColIA1 has been established during osteoblast differentiation, there is a proliferation phase. In this phase, osteoblast progenitors show alkaline phosphatase ALP activity, and are considered preosteoblasts [ 22 ]. Moreover, the osteoblasts undergo morphological changes, becoming large and cuboidal cells [ 26 , 29 — 31 ]. There is evidence that other factors such as fibroblast growth factor FGF , microRNAs, and connexin 43 play important roles in the osteoblast differentiation [ 32 — 35 ].
FGF-2 knockout mice showed a decreased bone mass coupled to increase of adipocytes in the bone marrow, indicating the participation of FGFs in the osteoblast differentiation [ 34 ].
It has also been demonstrated that FGF upregulates osteoblast differentiation in an autocrine mechanism [ 36 ]. MicroRNAs are involved in the regulation of gene expression in many cell types, including osteoblasts, in which some microRNAs stimulate and others inhibit osteoblast differentiation [ 37 , 38 ].
Connexin 43 is known to be the main connexin in bone [ 35 ]. The mutation in the gene encoding connexin 43 impairs osteoblast differentiation and causes skeletal malformation in mouse [ 39 ]. The synthesis of bone matrix by osteoblasts occurs in two main steps: deposition of organic matrix and its subsequent mineralization Figures 1 b — 1 d.
In the first step, the osteoblasts secrete collagen proteins, mainly type I collagen, noncollagen proteins OCN, osteonectin, BSP II, and osteopontin , and proteoglycan including decorin and biglycan, which form the organic matrix. Thereafter, mineralization of bone matrix takes place into two phases: the vesicular and the fibrillar phases [ 40 , 41 ]. Because of its negative charge, the sulphated proteoglycans immobilize calcium ions that are stored within the matrix vesicles [ 41 , 42 ].
When osteoblasts secrete enzymes that degrade the proteoglycans, the calcium ions are released from the proteoglycans and cross the calcium channels presented in the matrix vesicles membrane.
These channels are formed by proteins called annexins [ 40 ]. On the other hand, phosphate-containing compounds are degraded by the ALP secreted by osteoblasts, releasing phosphate ions inside the matrix vesicles. Then, the phosphate and calcium ions inside the vesicles nucleate, forming the hydroxyapatite crystals [ 43 ]. The fibrillar phase occurs when the supersaturation of calcium and phosphate ions inside the matrix vesicles leads to the rupture of these structures and the hydroxyapatite crystals spread to the surrounding matrix [ 44 , 45 ].
Mature osteoblasts appear as a single layer of cuboidal cells containing abundant rough endoplasmic reticulum and large Golgi complex Figures 2 a and 3 a. Some of these osteoblasts show cytoplasmic processes towards the bone matrix and reach the osteocyte processes [ 46 ].
At this stage, the mature osteoblasts can undergo apoptosis or become osteocytes or bone lining cells [ 47 , 48 ]. These findings suggest that besides professional phagocytes, osteoblasts are also able to engulf and degrade apoptotic bodies during alveolar bone formation [ 49 ]. Bone lining cells are quiescent flat-shaped osteoblasts that cover the bone surfaces, where neither bone resorption nor bone formation occurs [ 50 ]. These cells exhibit a thin and flat nuclear profile; its cytoplasm extends along the bone surface and displays few cytoplasmic organelles such as profiles of rough endoplasmic reticulum and Golgi apparatus [ 50 ] Figure 2 b.
Some of these cells show processes extending into canaliculi, and gap junctions are also observed between adjacent bone lining cells and between these cells and osteocytes [ 50 , 51 ]. The secretory activity of bone lining cells depends on the bone physiological status, whereby these cells can reacquire their secretory activity, enhancing their size and adopting a cuboidal appearance [ 52 ]. Bone lining cells functions are not completely understood, but it has been shown that these cells prevent the direct interaction between osteoclasts and bone matrix, when bone resorption should not occur, and also participate in osteoclast differentiation, producing osteoprotegerin OPG and the receptor activator of nuclear factor kappa-B ligand RANKL [ 14 , 53 ].
Moreover, the bone lining cells, together with other bone cells, are an important component of the BMU, an anatomical structure that is present during the bone remodeling cycle [ 9 ]. Different from osteoblasts and osteoclasts, which have been defined by their respective functions during bone formation and bone resorption, osteocytes were earlier defined by their morphology and location. For decades, due to difficulties in isolating osteocytes from bone matrix led to the erroneous notion that these cells would be passive cells, and their functions were misinterpreted [ 55 ].
The development of new technologies such as the identification of osteocyte-specific markers, new animal models, development of techniques for bone cell isolation and culture, and the establishment of phenotypically stable cell lines led to the improvement of the understanding of osteocyte biology.
In fact, it has been recognized that these cells play numerous important functions in bone [ 8 ]. The osteocytes are located within lacunae surrounded by mineralized bone matrix, wherein they show a dendritic morphology [ 15 , 55 , 56 ] Figures 3 a — 3 d.
The morphology of embedded osteocytes differs depending on the bone type. For instance, osteocytes from trabecular bone are more rounded than osteocytes from cortical bone, which display an elongated morphology [ 57 ]. Osteocytes are derived from MSCs lineage through osteoblast differentiation.
In this process, four recognizable stages have been proposed: osteoid-osteocyte, preosteocyte, young osteocyte, and mature osteocyte [ 54 ]. At the end of a bone formation cycle, a subpopulation of osteoblasts becomes osteocytes incorporated into the bone matrix. This process is accompanied by conspicuous morphological and ultrastructural changes, including the reduction of the round osteoblast size.
The number of organelles such as rough endoplasmic reticulum and Golgi apparatus decreases, and the nucleus-to-cytoplasm ratio increases, which correspond to a decrease in the protein synthesis and secretion [ 58 ]. The mechanisms involved in the development of osteocyte cytoplasmic processes are not well understood. Once the stage of mature osteocyte totally entrapped within mineralized bone matrix is accomplished, several of the previously expressed osteoblast markers such as OCN, BSPII, collagen type I, and ALP are downregulated.
On the other hand, osteocyte markers including dentine matrix protein 1 DMP1 and sclerostin are highly expressed [ 8 , 62 — 64 ]. Whereas the osteocyte cell body is located inside the lacuna, its cytoplasmic processes up to 50 per each cell cross tiny tunnels that originate from the lacuna space called canaliculi, forming the osteocyte lacunocanalicular system [ 65 ] Figures 3 b — 3 d.
These cytoplasmic processes are connected to other neighboring osteocytes processes by gap junctions, as well as to cytoplasmic processes of osteoblasts and bone lining cells on the bone surface, facilitating the intercellular transport of small signaling molecules such as prostaglandins and nitric oxide among these cells [ 66 ].
In addition, the osteocyte lacunocanalicular system is in close proximity to the vascular supply, whereby oxygen and nutrients achieve osteocytes [ 15 ]. It has been estimated that osteocyte surface is fold larger than that of the all Haversian and Volkmann systems and more than fold larger than the trabecular bone surface [ 67 , 68 ].
The cell-cell communication is also achieved by interstitial fluid that flows between the osteocytes processes and canaliculi [ 68 ]. By the lacunocanalicular system Figure 3 b , the osteocytes act as mechanosensors as their interconnected network has the capacity to detect mechanical pressures and loads, thereby helping the adaptation of bone to daily mechanical forces [ 55 ].
By this way, the osteocytes seem to act as orchestrators of bone remodeling, through regulation of osteoblast and osteoclast activities [ 15 , 69 ]. Moreover, osteocyte apoptosis has been recognized as a chemotactic signal to osteoclastic bone resorption [ 70 — 73 ].
In agreement, it has been shown that during bone resorption, apoptotic osteocytes are engulfed by osteoclasts [ 74 — 76 ]. The mechanosensitive function of osteocytes is accomplished due to the strategic location of these cells within bone matrix.
Thus, the shape and spatial arrangement of the osteocytes are in agreement with their sensing and signal transport functions, promoting the translation of mechanical stimuli into biochemical signals, a phenomenon that is called piezoelectric effect [ 77 ]. The mechanisms and components by which osteocytes convert mechanical stimuli to biochemical signals are not well known.
However, two mechanisms have been proposed. The second mechanism involves osteocyte cytoskeleton components, including focal adhesion protein complex and its multiple actin-associated proteins such as paxillin, vinculin, talin, and zyxin [ 79 ]. Independently of the mechanism involved, it is important to mention that the mechanosensitive function of osteocytes is possible due to the intricate canalicular network, which allows the communication among bone cells. Osteoclasts are terminally differentiated multinucleated cells Figures 4 a — 4 d , which originate from mononuclear cells of the hematopoietic stem cell lineage, under the influence of several factors.
Among these factors the macrophage colony-stimulating factor M-CSF , secreted by osteoprogenitor mesenchymal cells and osteoblasts [ 81 ], and RANK ligand, secreted by osteoblasts, osteocytes, and stromal cells, are included [ 20 ].
Together, these factors promote the activation of transcription factors [ 81 , 82 ] and gene expression in osteoclasts [ 83 , 84 ]. M-CSF binds to its receptor cFMS present in osteoclast precursors, which stimulates their proliferation and inhibits their apoptosis [ 82 , 85 ].
RANKL is a crucial factor for osteoclastogenesis and is expressed by osteoblasts, osteocytes, and stromal cells. When it binds to its receptor RANK in osteoclast precursors, osteoclast formation is induced [ 86 ].
By interacting with the transcription factors PU. Despite these osteoclastogenic factors having been well defined, it has recently been demonstrated that the osteoclastogenic potential may differ depending on the bone site considered. It has been reported that osteoclasts from long bone marrow are formed faster than in the jaw. This different dynamic of osteoclastogenesis possibly could be, due to the cellular composition of the bone-site specific marrow [ 93 ].
During bone remodeling osteoclasts polarize; then, four types of osteoclast membrane domains can be observed: the sealing zone and ruffled border that are in contact with the bone matrix Figures 4 b and 4 d , as well as the basolateral and functional secretory domains, which are not in contact with the bone matrix [ 94 , 95 ]. Polarization of osteoclasts during bone resorption involves rearrangement of the actin cytoskeleton, in which an F-actin ring that comprises a dense continuous zone of highly dynamic podosome is formed and consequently an area of membrane that develop into the ruffled border is isolated.
Physiology of normal bone marrow
Bones are an important part of the musculoskeletal system. This article, the first in a two-part series on the skeletal system, reviews the anatomy and physiology of bone. The skeletal system is formed of bones and cartilage, which are connected by ligaments to form a framework for the remainder of the body tissues. This article, the first in a two-part series on the structure and function of the skeletal system, reviews the anatomy and physiology of bone. Understanding the structure and purpose of the bone allows nurses to understand common pathophysiology and consider the most-appropriate steps to improve musculoskeletal health.
The musculoskeletal system is an organ system that enables an organism to move, support itself, and maintain stability during locomotion. The musculoskeletal system also known as the locomotor system is an organ system that gives animals including humans the ability to move, using the muscular and skeletal systems. It provides form, support, stability, and movement to the body. Its primary functions include supporting the body, allowing motion, and protecting vital organs. The bones of the skeletal system provide stability to the body analogous to a reinforcement bar in concrete construction. Muscles keep bones in place and also play a role in their movement.
Request PDF | Νormal Bone Marrow: Anatomy, Function, Conversion, and Reconversion | Bone marrow is the organ responsible for blood cell.
Bone marrow and the immune system
Bones are more than just the scaffolding that holds the body together. Bones come in all shapes and sizes and have many roles. In this article, we explain their function, what they are made of, and the types of cells involved. Bones have many functions. They support the body structurally, protect our vital organs, and allow us to move.
Bone tissue is continuously remodeled through the concerted actions of bone cells, which include bone resorption by osteoclasts and bone formation by osteoblasts, whereas osteocytes act as mechanosensors and orchestrators of the bone remodeling process. This process is under the control of local e. An imbalance between bone resorption and formation can result in bone diseases including osteoporosis.
Bone marrow is a semi-solid tissue found within the spongy or cancellous portions of bones.
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