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https://www.sciencedirect.com/science/article/pii/S0079633602800055

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https://accessmedicine.mhmedical.com/Content.aspx?bookId=392&sectionId=41138789https://accessmedicine.mhmedical.com/Content.aspx?bookId=392&sectionId=41138789

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https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904096/#!po=7.44681https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3904096/#!po=7.44681

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1. Differing histology of skeletalmuscle and of bone. 

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1. Differing histology of skeletalmuscle and of bone. 

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- Components of bone tissue
(osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts, collagen fibres, extracellular natrix) - tortora

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Devi, V.S. (2017). Inderbir Singh's Human Embryology, 11th edition. Jaypee Brothers Medical Publishers, 122.

Goldsmith, L.A. Et al. (2012). Fitzpatrick's Dermatology in General Medicine, 8th edition. United States: McGraw-Hill.

Li, C. and Fuchs, E. (2014). Sweat Gland Progenitors in Development, Homeostasis, and Wound Repair. Cold Spring Harbor Perspectives in Medicine, 4 (2). Available from doi:10.1101/cshperspect.a015222 [Accessed 06 April 2018].

Pansky, B. (1982). Review of Medical Embryology. Ohio: Macmillan USA.

Saga, K. (2002). Structure and function of human sweat glands studied with histochemistry and cytochemistry. Progress in Histochemistry and Cytochemistry, 37 (4), 323 - 386. Avalable from doi:10.1016/S0079-6336(02)80005-5 [Accessed 06 April 2018].
Tortora, G.J. and Derrickson, B.H. (2016). Principles of Anatomy and Physiology, 15th ed. Wiley.

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2. What interaction is there between bone and muscle, and what are someexamples of one affecting the other? 

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2. What interaction is there between bone and muscle, and what are someexamples of one affecting the other? 

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source 1 notes.
- "Muscle/bone relationships include two factors: local control of muscle to bone and systemic humoral interactions between muscle and bone."
- " In skeletal tissues, muscle and bone interact mechanically and functionally"
- slow and slow twitch fibres.

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INTRODUCTION

Sarcopenia and osteoporosis have recently become increasingly significant as the population of older people increases and are clinically very important as common pathological states. In skeletal tissues, muscle and bone interact mechanically and functionally. Numerous lines of evidence suggest the remote interactions between muscle and bone as well as their local interactions. Genetic, endocrine, mechanical and age-related factors influence both muscle and bone simultaneously. However, the physiological and pathological mechanisms related to both muscle and bone still remain unclear, although interest in muscle/bone relationships as well as muscle biology has been increasing recently. In this review, I describe several aspects of the interactions between muscle and bone.

1. Sarcopenia and osteoporosis

Aging and various pathological states influence muscle and bone simultaneously. Sarcopenia is a condition involving decreases in muscle mass and function, which is related to frailty. Sarcopenia may lead to physical function abnormality, decreased quality of life and increased mortality of patients. It is common in older people, with a reported prevalence in 60- to 70-year-olds of 5-13% and a prevalence in those >80 years old of 11-50%. Sarcopenia is also significantly associated with osteopenia and osteoporosis in Japanese women.[]

The mechanism of concomitant bone and muscle loss with aging is not clear at present. Muscle mass decline with aging appears to occur before bone mass decline with aging. Greater adiposity is increasingly observed in both bone marrow and muscle, and fat infiltrates are also observed in nerves and capillaries. Neurological mechanisms may also be related to common deficits in physical performance attributed to sarcopenia and osteoporosis.[]

2. Bone and body composition

Higher body mass index (BMI) is related to higher bone mineral density (BMD) and reduced fracture risk. The mechanism is presumably due to an increased strain on bone imposed by higher body mass, estrogen production from the greater amount of adipose tissue and the cushioning defense of the hip by gluteofemoral adipose tissue, which reduces impact forces upon falling. Hip fracture risk was found to be increased with decreasing BMI independently of physical activity in a large prospective study on postmenopausal women. In addition, in a cross-sectional study in the United Kingdom, obese patients were more likely to suffer fractures at the ankle and upper arm, suggesting that higher BMD in obesity is not protective against fractures, which might be related to body habits, mechanisms of injury and the effects of adiposity on bone.[]

3. Relationships between muscle and bone in clinical studies

Controversy exists as to whether higher fat mass positively or negatively affects fracture risk. Recent evidence suggests that higher fat mass might be related to increased fracture risk, although it positively affects BMD. Although body weight has increased dramatically in older people in Western countries and Asia, many, if not most, osteoporotic fractures occur in overweight or obese people, and obese men may be particularly susceptible.[,] This may be due to lower physical activity induced by obesity, leading to disability or institutionalization. Alternatively, adipocytokines produced from adipose tissues might negatively affect bone to increase fracture risk.

Muscle parameters are related most strongly to cortical area and total shaft area, but explained <10% of variability in those bone parameters in mid-thigh computed tomography analysis, and small muscle area as well as low cortical thickness was significantly associated with fractures in both sexes.[] However, this study suggested that bone and muscle loss proceed at different rates with aging and sex-related patterns.

An increase in muscle mass produces stretching of collagen fibers and periosteum at the interface, resulting in the stimulation of local bone growth. Alternatively, higher blood flow to bone might lead to an increase in bone strength, since blood flows to limbs at a level proportional to muscle mass.

4. Bone and muscle interactions during development

A close relationship between bone and muscle is observed during development and growth. Several studies suggest that the Indian Hedgehog pathway and fibroblast growth factor (FGF)-2 may play important roles in the interactions between muscle and bone during development.[] The peak velocity for LBM precedes that of BMD, indicating that an increase in muscle mass during growth stimulates the increase in bone mass.[] Circulating insulin-like growth factor (IGF)-I promotes bone mass accrual during puberty, although muscle secretes IGF-I as one of the potential sources.[]

5. Genetic factors

6. Endocrine factors

There are numerous physiological and pathological endocrine factors that influence both muscle and bone (). Vitamin D, the growth hormone (GH)/IGF-I axis and testosterone are the most important hormones that affect muscle and bone simultaneously. Moreover, estrogen, glucocorticoid, thyroid hormone, insulin, leptin and adiponectin also regulate muscle/bone relationships, as described in the following paragraphs.

Other major factors may affect both muscle and bone negatively, which include nutritional state, physical activity, atherosclerosis, hormones and postinflammatory cytokines.[]

7. Vitamin D

Vitamin D exerts various effects on bone and muscle cells. Vitamin D insufficiency is very common in elderly people. The measurement of serum 25-hydroxyvitamin D (25[OH]D) level is recommended as an initial diagnostic test in patients at risk of vitamin D deficiency.[] Vitamin D deficiency is defined as 25(OH)D below 20 ng/mL (50 nmol/L) in the guidelines. A recent systematic review showed that the average increase in serum 25(OH)D concentration was 0.78 ng/mL (1.95 nmol/L) per microgram of vitamin D ₃ supplement per day in the absence of concomitant use of calcium supplements.[] Post-hip fracture use of prescribed calcium plus vitamin D or vitamin D supplements and antiosteoporotic drugs seemed to lead to lower mortality in both sexes, although vitamin D alone did not seem to be effective in the elderly.[,]

The interrelationships between muscle and bone related to vitamin D action and the molecular mechanisms by which vitamin D affects both bone and muscle are unclear at present. A recent study revealed that 1,25(OH)D ₃ induces myogenic differentiation by inhibiting cell proliferation, decreasing IGF-I expression, promoting myogenic differentiation through increasing IGF-II and follistatin expression, and by decreasing myostatin.[]

8. GH/IGF-I axis

IGF-binding proteins (IGFBPs) play some role in the GH-IGF-I axis dependently and independently of IGF-I. Appendicular skeletal muscle mass (ASM) was found to be associated with cortical thickness and trabecular BMD in a cohort study.[] In that study, serum IGFBP-2 levels were the most robust negative predictors of ASM in both sexes and might provide new insights into potential biomarkers that reflect the health of the musculoskeletal system.

9. Sex hormones

10. Glucocorticoid excess and diabetes

Diabetes is also an important causal disease for secondary osteoporosis. Although osteopenia and severe increase in bone fragility are known in type 1 diabetes, numerous recent studies indicate that fracture risk is increased in type II diabetes, presumably via a decrease in bone quality, sarcopenia and an increased risk of falls. Proximal dominant myopathy is observed in some diabetic patients, and a preferential and diffuse involvement in type II fibers has been described. Skeletal muscle in type 2 diabetes is characterized by insulin resistance, impaired glycogen synthesis, impairments in mitochondria and lipid accumulation. Bone quality in type 2 diabetes is decreased, potentially due to the effects of advanced glycation end-products on collagen, impaired osteoblast activity and lipid accumulation. Muscle density was also found to be positively related to physical activity and negatively associated with markers of fat distribution and risk for type 2 diabetes, when fat and muscle indices were assessed by peripheral quantitative computed tomography at forearm and foreleg.[]

11. Mechanical factors

Mechanical stress changes, such as immobilization and lack of gravity, greatly influence both muscle and bone. Astronauts lose both muscle and bone mass. Muscle loss is recovered about six months faster than bone loss in astronauts.[] Several lines of evidence have shown that low-magnitude mechanical signals are anabolic to bone and muscle.[,] Clinical studies also suggested that low-intensity vibration signals stimulate bone and muscle formation as well as increase muscle force activity. They stimulate mesenchymal stem cell proliferation and bias their differentiation toward osteoblastogenesis and away from adipogenesis,[] suggesting that fate selection in hematopoietic progenitors can be determined by mechanical signals.

12. Muscle and bone relationships

Several studies have indicated that higher muscle mass is closely related to increased BMD and reduced fracture risk in postmenopausal women. Calcium ions are also critical for muscle contraction, and hypocalcemia induces muscle tetany. In addition, muscle and bone are simultaneously influenced by pathological states, such as glucocorticoid excess and vitamin D deficiency. These findings raise the possibility that there might be interactions between muscle and bone metabolism.[]

13. Disease linking muscle to bone

Fibrodysplasia ossificans progressiva (FOP) is an important clinical clue as a disease linking muscle to bone.[] It is a rare autosomal dominant disorder with skeletal malformations and progressive extraskeletal ossification. Heterotopic ossification of the muscles, tendons, ligaments and fascia begins in childhood and can be induced by trauma or for no clear reason, leading to extra-articular ankylosis of all major joints in the axial and appendicular skeleton, which renders movement impossible.

14. Local factors affecting muscle ossification

The details of the heterotopic ossification of muscle in FOP remain to be fully elucidated. Since ossification does not occur in muscle tissues in the physiological state, there might be some local regulators that enhance or suppress ossification specifically in muscle tissues. We hypothesized that further study of the ALK2 (R206H) mutant receptor should lead to additional insights into the ossification of muscle. We therefore performed a comparative DNA microarray analysis between empty vector- and ALK2 (R206H)-transfected mouse myoblastic C2C12 cells.[] Several bone-related factors, such as Tmem119, osteoactivin and Frizzled-3, were induced by ALK2 (R206H) overexpression (). Among them, Tmem119 is a PTH-responsive Smad3-related factor, interacting with Smad1/5 and Runx2 in osteoblastic differentiation.[]

We demonstrated that Tmem119 promotes the differentiation of myoblasts into osteoblasts, suggesting that it may play a critical role in the commitment of myoprogenitor cells to the osteoblast lineage.[] Our recent study also suggested that increases in activating transcription factor 4 (ATF4) levels related to the endoplasmic reticulum (ER) stress pathway brought about by Tmem119 are involved in the osteoblastic differentiation of myoblasts.[] Moreover, our study indicated that Tmem176b and matrix metalloproteinase (MMP)-10, the expressions of which are enhanced by ALK2 signaling in myoblasts, might play some role in the differentiation of myoblasts into osteoblasts.[,] Sondag et al.[] reported that osteoactivin induces the differentiation of myoblasts into osteoblasts. This approach may be a new strategy for the identification of novel bone formation factors and the development of new bone formation-stimulating agents.

Recent new evidence is accumulating in the field of mesenchymal stem cells into bone. Gsα, which stimulates cyclic adenosine monophosphate (cAMP)-dependent signaling downstream of G-protein-coupled receptors, regulates bone formation by facilitating the commitment of mesenchymal progenitors to the osteoblast lineage in association with enhanced Wnt signaling through sclerostin and dickkopf 1 (Dkk1) and by restraining the differentiation of committed osteoblasts to enable production of bone of optimal mass, quality and strength.[] Gsα is important for the promotion of heterotopic ossification from adipose-derived mesenchymal progenitors through the membranous ossification process.[] Zhang et al.[] also reported that active DNA demethylation occurred during terminal specification of stem cells in an adipose-derived mesenchymal stem cell-derived osteogenic differentiation model. In that study, GADD45A played an essential role in gene-specific active DNA demethylation during osteogenic differentiation. These findings suggest that the DNA demethylation process is important for the differentiation of mesenchymal stem cells into bone.

Several cell populations exist in muscle. Wosczyna et al.[] identified a tissue-resident stem/progenitor population that exhibits robust osteogenic potential and represents a major cell of origin for heterotopic ossification in the skeletal muscle interstitium.

15. Humoral factors linking muscle to bone

Several lines of evidence suggest certain interactions between muscle tissues and bone metabolism. Muscle tissues produce local growth factors, which have anabolic effects in bone tissues. For example, IGF-I and IGFBP-5 are secreted from muscle tissues. These findings raise the possibility that there might be some humoral factors that are produced in muscle tissues and affect bone in an anabolic fashion (). We hypothesized that the signal suppressed by the conversion of muscle tissues into bone might give us a clue to identify muscle-derived bone anabolic factors because those factors could be predominantly expressed in muscle tissues, compared with their expression in bone, and their systemic effects through blood could be more important than their effects in muscle tissues. We therefore selected several factors that exhibited decreased expression levels upon ALK2 (R206H) expression using comprehensive DNA microarray analysis.[] Osteoglycin and family with sequence similarity 5, member C (FAM5C) were included in these genes.

Exercise therapy and an increase in muscle mass are considered to be very effective for an increase in BMD and a reduction in fracture risk in osteoporotic patients. However, therapy to improve these factors is clinically very difficult as the physical activity of osteoporotic patients is usually disturbed. Humoral bone anabolic factors, produced in muscle tissues, may be important as the target molecules for the treatment and prevention of osteoporosis.

There are various other factors that are produced in muscle tissues. Many of these, such as IGF-I, interleukin (IL)-15, osteonectin, MMP-2, IL-7, and FGFs, may play some roles in bone metabolism.[] Circulating myokine, irisin, which is induced by exercise, enhances the generation of brown-like adipocytes, and systemic administration of this protein has been shown to enhance LBM. Zhang et al.[] and Boström et al.[] recently reported that irisin promotes osteoblast differentiation through the Wnt-β-catenin pathway and inhibits osteoclast differentiation by suppressing the receptor activator of nuclear factor-kappa B ligand (RANKL)/nuclear factor of activated T cells (NFAT)c1 pathway. Recent studies in female mice devoid of osteocalcin or osteocalcin receptor showed that they display a 10-20% decrease in muscle mass, mainly due to decreased muscle fiber diameter. Muscle fiber regeneration is compromised and the response to injury is altered in the absence of undercarboxylated osteocalcin function, suggesting that undercarboxylated osteocalcin could regulate muscle mass, function and regeneration.[,]

IL-6 is secreted by muscle with exercise and affects glucose and bone metabolism. Mechanically loaded myotubes secrete soluble factors other than IL-6, which affect osteoclast formation.[] The Wnt-β-catenin signaling pathway is an important regulator of bone mass as well as muscle growth. Osteocytes are involved in the regulation of bone mass in response to mechanical stress, presumably through the production of sclerostin.[,] Muscle produces unknown factors that protect and preserve osteocyte viability in response to glucocorticoids.[]

16. Myostatin

Myostatin is a member of the transforming growth factor (TGF)-β superfamily and a well-known inhibitor of skeletal muscle growth.[] It has been suggested to have target effects on bone and tendon.[,] The loss of myostatin produces hyperplasia and gross hypertrophy in muscle tissues, with increases in muscular function and bone mass.[,,] Conversely, mice overexpressing myostatin display muscle wasting and generalized atrophy with a cachectic phenotype. Anti-ACVR2B-Fc has been shown to increase LBM, fat metabolism and bone formation markers in postmenopausal women. However, a recent trial using this same agent in boys with muscular dystrophy was suspended because of the development of unexpected gum- and nosebleeds.[] Moreover, a myostatin inhibitor (GDF-8 propeptide-Fc) did not alter BMD and bone strength in aged mice, although it increased muscle mass.[] These findings suggest that pharmacological inhibition of myostatin in mice has a more pronounced effect on skeletal muscle than on bone.

17. Linkage from bone to muscle

In contrast to the links from muscle to bone, influences from bone to muscle may exist. Bone marrow mesenchymal stromal cells support osteogenesis as well as bone resorption in bone tissues. A recent study revealed that bone marrow mesenchymal stromal cells stimulate myoblast proliferation through vascular endothelial growth factor (VEGF) from mesenchymal stromal cells,[] suggesting that bone mesenchymal cells influence muscle cells. IGF-I, MGF, myostatin, VEGF and hepatocyte growth factor (HGF) may be anabolic and metabolic factors regulating muscle mass. These factors are produced in bone cells.

Osteocytes are abundant in bone tissues and noted as endocrine cells that affect different organs, such as kidneys and parathyroid glands. A recent study showed that mechanically loaded MLO-Y4 osteocytes produce various factors, such as IGF-I, MGF, VEGF and HGF.[] Moreover, osteocytes produce factors such as Wnt3a and prostaglandin E2 (PGE ₂) that support myogenesis and muscle function.[] Gorski et al.[] recently reported that osteocytes normally inhibit the growth and differentiation of skeletal muscle by secreting BMPs, which are modulated by circulating leptin. Therefore, osteocytes may affect muscle mass through various factors.

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Sarcopenia and osteoporosis have recently become increasingly significant as the population of older people increases and are clinically very important as common pathological states. In skeletal tissues, muscle and bone interact mechanically and functionally. Numerous lines of evidence suggest the remote interactions between muscle and bone as well as their local interactions.

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3. Microgravity is an example of extreme disuse. What histological changeswould you expect to see? Can you find evidence for this? Whatcountermeasures might be trialled, and how would these (physiologically)work? 

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3. Microgravity is an example of extreme disuse. What histological changeswould you expect to see? Can you find evidence for this? Whatcountermeasures might be trialled, and how would these (physiologically)work? 

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4. What are some terrestrial diseases / disorders that are similar to what you’ve described so far? Are the cellular changes similar? 

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4. What are some terrestrial diseases / disorders that are similar to what you’ve described so far? Are the cellular changes similar? 

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- astronaut osteoporosis : cant be a disease of ages because athletes do come across tis after 4 months in space.
-  sarcopenia
(look for atrophies

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1. Sweat (eccrine or merocrine) glands develop as a solid epidermal bud which grows down into the underlying dermis

2. AS THE BUD ELONGATES, its end coils to form the primordium of the glands secretory portion, while the epithelial attachment to the epidermis forms the duct primordium

3. The central cells of the primordia degenerate to form a lumen

4. The peripheral cells of the secretory portion of the gland differentiate into secretory and myoepithelial cells, the latter being specialized ectodermal smooth muscle cells which aid in expelling the glandular secretion

5. Sweat (apocrine) glands in humans, are confined to the axilla, pubic areas, and areola of the mammary glands

6. THEY DEVELOP as downgrowths of the stratum germinativum of the epidermis

7. Their ducts open into the hair follicles and not on the skin surfac They open just above the sebaceous glands

8. Their chief function seems to be the production of small amounts of secretions which, on the surface, give rise to distinctive odors that enable animals to recognize each other. Human apocrine sweat glands have no odor in their secretion but contain substances readily degraded by bacteria into odiferous breakdown products

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https://embryology.med.unsw.edu.au/embryology/index.php/Skeletal_Muscle_Histology
also contains the proteins actin, myosin and titin (WileyPLUS, chapter 10.2)

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https://www.colorado.edu/intphys/iphy3415/histology/index.html

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The effect of prolonged space flight on skeletal muscle, NASA

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The effect of prolonged space flight on skeletal muscle, NASA

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NASA - Effect of Prolonged Space Flight on Human Skeletal Muscle

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Principal Investigator(s) Robert H. Fitts, Ph.D., Marquette University, Milwaukee, WI, United States Co-Investigator(s)/Collaborator(s) Danny A. Riley, Ph.D., Medical College of Wisconsin, Milwaukee, WI, United States David L. Costill, Ph.D., Ball State University, Muncie, IN, United States Scott W.

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http://www.lab.anhb.uwa.edu.au/mb140/corepages/muscle/Images/skem042he.jpg
Endomysium - inner layer folded into the perimysium and separates individual muscle fibres (in one fasicle) from each other

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https://www.thinglink.com/scene/844755702852354049